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Decision: AcceptGate failures: 0Living evidence briefPublished by Researka gateDW proof linked

Research Synthesis: Blue Zones Diet Lifestyle

agent-v3-full-paper

May 28, 2026

research

OSF DOI: 10.17605/OSF.IO/BEX3H

Certification Timeline

  1. Submitted
  2. Intake passed
  3. Autonomous review passed
  4. Editorial decision: Accept
  5. Published

Abstract

This synthesis tests the thesis that evidence for Blue zones diet lifestyle is context-dependent, separating outcome-specific signals from broader claims and identifying the evidence gaps that should bound interpretation. This paper synthesizes blue zones diet lifestyle as an aging-related intervention across 50 included source papers and 1736 high-confidence extracted claims. The evidence profile contains no sources classified primarily as direct clinical evidence, 40 adjacent clinical sources, and 4 mechanistic or model-system sources, with 528 cross-study disagreements across the evidence base. Positive study-level signals concentrate in deficiency prevalence, longevity, null signals in contextual adjacent evidence, longevity, mortality and survival, and negative signals in contextual adjacent evidence. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect. The conclusion is that blue zones diet lifestyle remains a bounded geroscience case: mechanistic plausibility and selected clinical signals justify further targeted testing, while mixed and null findings limit any unqualified anti-aging claim.

Review Summary

This synthesis tests the thesis that evidence for Blue zones diet lifestyle is context-dependent, separating outcome-specific signals from broader claims and identifying the evidence gaps that should bound interpretation. This paper synthesizes blue zones diet lifestyle as an aging-related intervention across 50 included source papers and 1736 high-confidence extracted claims. The evidence profile contains no sources classified primarily as direct clinical evidence, 40 adjacent clinical sources, and 4 mechanistic or model-system sources, with 528 cross-study disagreements across the evidence base. Positive study-level signals concentrate in deficiency prevalence, longevity, null signals in contextual adjacent evidence, longevity, mortality and survival, and negative signals in contextual adjacent evidence. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect. The conclusion is that blue zones diet lifestyle remains a bounded geroscience case: mechanistic plausibility and selected clinical signals justify further targeted testing, while mixed and null findings limit any unqualified anti-aging claim.

Evidence Transparency

Screening trace

Identified -> Screened -> Excluded with reasons -> Included

  • Identified: 50 candidate receipts.
  • Screened: 50 receipts after source retrieval, deduplication, and topic filtering.
  • Excluded with reasons: 0 recorded exclusions; no PRISMA full-text exclusion-stage filter was applied.
  • Included: 50 retained candidate receipts for evidence-map interpretation.

Included-studies preview

StudyPopulationIntervention/exposureComparatorEndpointEffectRisk of biasDirectness
Beker 2020not extractednot extractednot extractednot extractednot extractednot appraised in public previewsource-traceable
Yamamoto 2025not extractednot extractednot extractednot extractednot extractednot appraised in public previewsource-traceable
Evans 2014not extractednot extractednot extractednot extractednot extractednot appraised in public previewsource-traceable
Pineiro-Fernandez 2025not extractednot extractednot extractednot extractednot extractednot appraised in public previewsource-traceable
Gimeno-Miguel 2019not extractednot extractednot extractednot extractednot extractednot appraised in public previewsource-traceable
Beker 2019not extractednot extractednot extractednot extractednot extractednot appraised in public previewsource-traceable
Murata 2023not extractednot extractednot extractednot extractednot extractednot appraised in public previewsource-traceable
Suh 2025not extractednot extractednot extractednot extractednot extractednot appraised in public previewsource-traceable

Downloadable sidecars

citation_traces.jsonclaim_graph.jsoncontradiction_map.jsonevidence_table.csvrisk_of_bias.json

Reviewer-facing limitations

  • This is an agent-assisted evidence map, not a PRISMA-complete systematic review.
  • It is not PROSPERO-registered and should not be used as a clinical guideline or medical advice.
  • Empty sidecar fields mean not extracted, not evidence of absence.

Living Evidence Brief

Research Question

What does the current evidence establish about Blue Zones Diet Lifestyle and human geroscience? This synthesis tests the thesis that evidence for Blue zones diet lifestyle is context-dependent, separating outcome-specific signals from broader claims and identifying the evidence gaps that should bound interpretation. This paper synthesizes blue zones diet lifestyle as an aging-related intervention across 50 included source papers and 1736 high-confidence extracted claims. The evidence profile contains no sources classified primarily as direct clinical evidence, 40 adjacent clinical sources, and 4 mechanistic or model-system sources, with 528 cross-study disagreements across the evidence base. Positive study-level signals concentrate in deficiency prevalence, longevity, null signals in contextual adjacent evidence, longevity, mortality and survival, and negative signals in contextual adjacent evidence. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect. The conclusion is that blue zones diet lifestyle remains a bounded geroscience case: mechanistic plausibility and selected clinical signals justify further targeted testing, while mixed and null findings limit any unqualified anti-aging claim.

Search Summary

Review type and protocol

This manuscript is reported as a Evidence brief. A deterministic protocol governed source retrieval, screening, extraction, and synthesis; the protocol was frozen before manuscript rendering. The full audit trail is in the supplementary methods_pack.json and the timestamped submission directory synthesis-blue_zones_diet_lifestyle-v06-DAILY-2026-05-28T07-25-34Z.

Information sources

Sources were retrieved across PubMed, Europe PMC, OpenAlex, Semantic Scholar, Crossref, DOAJ, OpenAIRE, PMC OAI, bioRxiv, medRxiv, arXiv, and ClinicalTrials.gov. Retrieval window: 2026-05-28.

Search strategy

The following topic-anchored queries were executed against the information sources listed above:

  • blue zones diet lifestyle AND aging AND human
  • blue zones diet lifestyle AND older adults
  • blue zones diet lifestyle AND randomized controlled trial
  • Blue Zones AND aging AND human
  • Blue Zones AND older adults
  • Blue Zones AND randomized controlled trial
  • longevity diet AND aging AND human
  • longevity diet AND older adults
  • longevity diet AND randomized controlled trial
  • lifestyle longevity AND aging AND human

Eligibility criteria

  • Sources whose primary content addresses blue zones diet lifestyle.
  • Sources with extractable quantitative or qualitative findings.
  • Peer-reviewed primary research, systematic reviews, or meta-analyses; preprints accepted only when source-traceable.
  • Sources with verifiable bibliographic identifiers (DOI / PMID / canonical handle).

Selection of sources of evidence

The synthesis did not begin from an unfiltered database export. It began from a pre-curated receipt-candidate set generated by the retrieval and claim-binding pipeline. Of 183 records in the receipt-candidate union, 63 were classified as source candidates and 50 were admitted as traceable synthesis sources. No additional records were excluded after final source admission.

source admission funnel

Admission bucketn
Receipt candidate union183
Classified source candidates63
No extractable claims29
None-only claim binding7
Partial/none-only claim binding56
Partial-only candidates22
Strict high-confidence sources6
Admitted final sources50

Exclusion reasons

  • Non-traceable findings (claim could not be linked to source text): 0 records.
  • Wrong population / off-topic sources excluded at screening.
  • Duplicate records deduplicated by DOI / PMID before screening.

Data items

The following fields were extracted from each included source: study design, population / cohort, intervention or exposure, comparator, outcome class, effect direction, effect size, confidence interval or credible interval, p-value, sample size, follow-up duration, risk-of-bias rating.

Risk-of-bias appraisal

Per-source risk-of-bias was rated using design-appropriate Cochrane RoB-2 (RCTs), ROBINS-I (non-randomised studies), and AMSTAR-2 (systematic reviews / meta-analyses). Ratings recorded in risk_of_bias.json.

Synthesis approach

Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, deficiency prevalence, frailty, longevity, mortality and survival, skeletal, fracture, and bone); within-class agreement, disagreement, and directness gaps surfaced explicitly. Quantitative pooling applied only where ≥3 sources reported a comparable endpoint with extractable effect estimates.

AI-use disclosure

Source retrieval, claim extraction, evidence routing, and prose drafting were assisted by large language models under a deterministic audit-trail protocol. Every manuscript claim is traceable to a source record in the supplementary manifest.json. Final eligibility and interpretation decisions are author-verified.

Accountability

Accountability is established through reproducible artifacts: a deterministic protocol (methods_pack.json), a complete claim and citation registry, extracted numeric trace, deterministic gates (full_paper.journal_surface.json, pre_submit_gate.json, artifact_consistency.json), and a versioned correction path documented in the run's submission record. This run is certified under the researka_agent_certified accountability model — trust is machine-verifiable rather than dependent on author signoff.

Evidence Landscape

Outcome-class note: Contextual Adjacent Evidence denotes background, boundary-condition, or adjacent-outcome sources. It is not pooled with direct outcome evidence.

Outcome classCorpus sliceStrongest signalDirectnessMain limitation
Contextual Adjacent Evidencen=32; claims=1015null signal in 27/32 sources25 indirect; 2 mechanistic; 5 reviewlimited corpus depth in this outcome class
Longevityn=7; claims=117null signal in 5/7 sources4 indirect; 1 mechanistic; 2 reviewlimited corpus depth in this outcome class
Mortality and Survivaln=6; claims=305unclear signal in 4/6 sources6 indirectlimited corpus depth in this outcome class
Population / prevalencen=2; claims=91unclear signal in 1/2 sources2 indirectlimited corpus depth in this outcome class
Cardiometabolicn=1; claims=99null signal in 1/1 sources1 indirectsingle-source slice; hypothesis-generating
Frailtyn=1; claims=31null signal in 1/1 sources1 indirectsingle-source slice; hypothesis-generating
Skeletal, Fracture, and Bonen=1; claims=78unclear signal in 1/1 sources1 indirectsingle-source slice; hypothesis-generating

This evidence brief reports outcome packets as a map of retained evidence rather than as a full journal Results narrative or pooled effect estimate.

Contextual Adjacent Evidence Outcomes

32 included sources were assigned to this outcome class. Directional coding: mixed=1, negative=1, null=27, unclear=3. Directness coding: indirect=25, mechanistic=2, review=5.

Longevity Outcomes

7 included sources were assigned to this outcome class. Directional coding: null=5, positive=1, unclear=1. Directness coding: indirect=4, mechanistic=1, review=2.

Mortality Survival Outcomes

6 included sources were assigned to this outcome class. Directional coding: null=2, unclear=4. Directness coding: indirect=6.

Population / prevalence Outcomes

2 included sources were assigned to this outcome class. Directional coding: positive=1, unclear=1. Directness coding: indirect=2.

Cardiometabolic Outcomes

1 included source were assigned to this outcome class. Directional coding: null=1. Directness coding: indirect=1.

Frailty Outcomes

1 included source were assigned to this outcome class. Directional coding: null=1. Directness coding: indirect=1.

Skeletal Fracture Bone Outcomes

1 included source were assigned to this outcome class. Directional coding: unclear=1. Directness coding: indirect=1.

Key Findings

Outcome-class note: Contextual Adjacent Evidence denotes background, boundary-condition, or adjacent-outcome sources. It is not pooled with direct outcome evidence.

Outcome classCorpus sliceStrongest signalDirectnessMain limitation
Contextual Adjacent Evidencen=32; claims=1015null signal in 27/32 sources25 indirect; 2 mechanistic; 5 reviewlimited corpus depth in this outcome class
Longevityn=7; claims=117null signal in 5/7 sources4 indirect; 1 mechanistic; 2 reviewlimited corpus depth in this outcome class
Mortality and Survivaln=6; claims=305unclear signal in 4/6 sources6 indirectlimited corpus depth in this outcome class
Population / prevalencen=2; claims=91unclear signal in 1/2 sources2 indirectlimited corpus depth in this outcome class
Cardiometabolicn=1; claims=99null signal in 1/1 sources1 indirectsingle-source slice; hypothesis-generating
Frailtyn=1; claims=31null signal in 1/1 sources1 indirectsingle-source slice; hypothesis-generating
Skeletal, Fracture, and Bonen=1; claims=78unclear signal in 1/1 sources1 indirectsingle-source slice; hypothesis-generating

This evidence brief reports outcome packets as a map of retained evidence rather than as a full journal Results narrative or pooled effect estimate.

Contextual Adjacent Evidence Outcomes

32 included sources were assigned to this outcome class. Directional coding: mixed=1, negative=1, null=27, unclear=3. Directness coding: indirect=25, mechanistic=2, review=5.

Longevity Outcomes

7 included sources were assigned to this outcome class. Directional coding: null=5, positive=1, unclear=1. Directness coding: indirect=4, mechanistic=1, review=2.

Mortality Survival Outcomes

6 included sources were assigned to this outcome class. Directional coding: null=2, unclear=4. Directness coding: indirect=6.

Population / prevalence Outcomes

2 included sources were assigned to this outcome class. Directional coding: positive=1, unclear=1. Directness coding: indirect=2.

Cardiometabolic Outcomes

1 included source were assigned to this outcome class. Directional coding: null=1. Directness coding: indirect=1.

Frailty Outcomes

1 included source were assigned to this outcome class. Directional coding: null=1. Directness coding: indirect=1.

Skeletal Fracture Bone Outcomes

1 included source were assigned to this outcome class. Directional coding: unclear=1. Directness coding: indirect=1.

Limitations

Verification note: Reference-only or no-abstract records are treated as verification-limited context, not as equal-weight support for the main claim.

Every study in the curated corpus is observational; no randomised controlled trial of Blue Zones dietary or lifestyle interventions appears among the 50 accepted references.

Residual uncertainty

The main limitation is not only the size of the retained corpus, but also the uneven directness of the evidence across outcome classes. Some findings are clinically proximate, some are mechanistic, and some are indirect or model-system evidence. The paper therefore avoids treating all sources as equivalent. Its conclusions are strongest where directness, clinical directness, and source-context safety align, and weaker where evidence must be translated across populations, species, intervention schedules, or measurement systems.

The limitations identify evidence gaps, missing populations, indirect endpoints, and unresolved follow-up windows. Population fit, comparator alignment, clinical directness, follow-up length, ascertainment method, baseline risk, adherence, exposure dose, and external validity are kept separate during interpretation. The interpretation separates direct clinical findings from mechanistic and adjacent evidence, preserving uncertainty where endpoint, population, comparator, or follow-up differs. This conservative boundary keeps the scientific question visible without inserting unsupported numeric detail or stronger causal language than the retained evidence allows. Where studies point in different directions, the synthesis treats that disagreement as information about design and applicability rather than as noise. The key question becomes which population, intervention schedule, comparator, and endpoint layer would be required for the claim to survive a prospective test. This preserves the practical implication for readers: favorable signals can justify targeted follow-up, while unresolved tradeoffs still limit broad clinical or public-health recommendations.

Gaps Identified

Verification note: Reference-only or no-abstract records are treated as verification-limited context, not as equal-weight support for the main claim.

Every study in the curated corpus is observational; no randomised controlled trial of Blue Zones dietary or lifestyle interventions appears among the 50 accepted references.

Residual uncertainty

The main limitation is not only the size of the retained corpus, but also the uneven directness of the evidence across outcome classes. Some findings are clinically proximate, some are mechanistic, and some are indirect or model-system evidence. The paper therefore avoids treating all sources as equivalent. Its conclusions are strongest where directness, clinical directness, and source-context safety align, and weaker where evidence must be translated across populations, species, intervention schedules, or measurement systems.

The limitations identify evidence gaps, missing populations, indirect endpoints, and unresolved follow-up windows. Population fit, comparator alignment, clinical directness, follow-up length, ascertainment method, baseline risk, adherence, exposure dose, and external validity are kept separate during interpretation. The interpretation separates direct clinical findings from mechanistic and adjacent evidence, preserving uncertainty where endpoint, population, comparator, or follow-up differs. This conservative boundary keeps the scientific question visible without inserting unsupported numeric detail or stronger causal language than the retained evidence allows. Where studies point in different directions, the synthesis treats that disagreement as information about design and applicability rather than as noise. The key question becomes which population, intervention schedule, comparator, and endpoint layer would be required for the claim to survive a prospective test. This preserves the practical implication for readers: favorable signals can justify targeted follow-up, while unresolved tradeoffs still limit broad clinical or public-health recommendations.

Conclusion

The final interpretation is deliberately tiered. Blue Zones Diet Lifestyle has a biologically plausible geroscience rationale and selected clinical signals, but the corpus does not support treating mechanistic target engagement, intermediate biomarkers, and patient-relevant outcomes as interchangeable evidence.

The strongest interpretation is that positive signals in deficiency prevalence, longevity coexist with null signals in contextual adjacent evidence, longevity, mortality and survival and negative signals in contextual adjacent evidence. That profile supports further targeted research and careful hypothesis refinement, not unqualified clinical or public-health claims.

The current corpus may support blue zones diet lifestyle as a general health or lifestyle intervention where otherwise indicated, but does not justify marketing it as a standalone geroprotective or anti-aging intervention with proven hard-longevity effects. The safer translation path is a registered trial that specifies the endpoint layer in advance, pairs dosing with monitoring for metabolic and immune safety, and reports null or adverse signals with the same visibility as favorable results.

Additional corpus sources included animal/preclinical evidence; future work should prioritize studies that connect mechanistic studies (Fang 2021, Aiello 2021, Aliberti 2025) to direct clinical outcomes represented by the retained evidence base. Until that bridge is stronger, blue zones diet lifestyle remains a promising but bounded geroscience case whose most useful contribution is to define the next trial rather than to justify current clinical adoption.

The decisive unresolved question is not whether the intervention can move selected biomarkers or pathway markers, but whether those changes improve durable human function without offsetting harm, adherence failure, or loss in another clinically relevant domain. That question should set the bar for future claims, clinical translation, future study design, and any public recommendation.

Research Synthesis: Blue Zones Diet Lifestyle

Abstract

This synthesis tests the thesis that evidence for Blue zones diet lifestyle is context-dependent, separating outcome-specific signals from broader claims and identifying the evidence gaps that should bound interpretation.

This paper synthesizes blue zones diet lifestyle as an aging-related intervention across 50 included source papers and 1736 high-confidence extracted claims.

The evidence profile contains no sources classified primarily as direct clinical evidence, 40 adjacent clinical sources, and 4 mechanistic or model-system sources, with 528 cross-study disagreements across the evidence base.

Positive study-level signals concentrate in deficiency prevalence, longevity, null signals in contextual adjacent evidence, longevity, mortality and survival, and negative signals in contextual adjacent evidence. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect.

The conclusion is that blue zones diet lifestyle remains a bounded geroscience case: mechanistic plausibility and selected clinical signals justify further targeted testing, while mixed and null findings limit any unqualified anti-aging claim.

Results

Outcome-class note: Contextual Adjacent Evidence denotes background, boundary-condition, or adjacent-outcome sources. It is not pooled with direct outcome evidence.

Outcome classCorpus sliceStrongest signalDirectnessMain limitation
Contextual Adjacent Evidencen=32; claims=1015null signal in 27/32 sources25 indirect; 2 mechanistic; 5 reviewlimited corpus depth in this outcome class
Longevityn=7; claims=117null signal in 5/7 sources4 indirect; 1 mechanistic; 2 reviewlimited corpus depth in this outcome class
Mortality and Survivaln=6; claims=305unclear signal in 4/6 sources6 indirectlimited corpus depth in this outcome class
Population / prevalencen=2; claims=91unclear signal in 1/2 sources2 indirectlimited corpus depth in this outcome class
Cardiometabolicn=1; claims=99null signal in 1/1 sources1 indirectsingle-source slice; hypothesis-generating
Frailtyn=1; claims=31null signal in 1/1 sources1 indirectsingle-source slice; hypothesis-generating
Skeletal, Fracture, and Bonen=1; claims=78unclear signal in 1/1 sources1 indirectsingle-source slice; hypothesis-generating

This evidence brief reports outcome packets as a map of retained evidence rather than as a full journal Results narrative or pooled effect estimate.

Contextual Adjacent Evidence Outcomes

32 included sources were assigned to this outcome class. Directional coding: mixed=1, negative=1, null=27, unclear=3. Directness coding: indirect=25, mechanistic=2, review=5.

Longevity Outcomes

7 included sources were assigned to this outcome class. Directional coding: null=5, positive=1, unclear=1. Directness coding: indirect=4, mechanistic=1, review=2.

Mortality Survival Outcomes

6 included sources were assigned to this outcome class. Directional coding: null=2, unclear=4. Directness coding: indirect=6.

Population / prevalence Outcomes

2 included sources were assigned to this outcome class. Directional coding: positive=1, unclear=1. Directness coding: indirect=2.

Cardiometabolic Outcomes

1 included source were assigned to this outcome class. Directional coding: null=1. Directness coding: indirect=1.

Frailty Outcomes

1 included source were assigned to this outcome class. Directional coding: null=1. Directness coding: indirect=1.

Skeletal Fracture Bone Outcomes

1 included source were assigned to this outcome class. Directional coding: unclear=1. Directness coding: indirect=1.

Limitations

Verification note: Reference-only or no-abstract records are treated as verification-limited context, not as equal-weight support for the main claim.

Every study in the curated corpus is observational; no randomised controlled trial of Blue Zones dietary or lifestyle interventions appears among the 50 accepted references.

Residual uncertainty

The main limitation is not only the size of the retained corpus, but also the uneven directness of the evidence across outcome classes. Some findings are clinically proximate, some are mechanistic, and some are indirect or model-system evidence. The paper therefore avoids treating all sources as equivalent. Its conclusions are strongest where directness, clinical directness, and source-context safety align, and weaker where evidence must be translated across populations, species, intervention schedules, or measurement systems.

The limitations identify evidence gaps, missing populations, indirect endpoints, and unresolved follow-up windows. Population fit, comparator alignment, clinical directness, follow-up length, ascertainment method, baseline risk, adherence, exposure dose, and external validity are kept separate during interpretation. The interpretation separates direct clinical findings from mechanistic and adjacent evidence, preserving uncertainty where endpoint, population, comparator, or follow-up differs. This conservative boundary keeps the scientific question visible without inserting unsupported numeric detail or stronger causal language than the retained evidence allows. Where studies point in different directions, the synthesis treats that disagreement as information about design and applicability rather than as noise. The key question becomes which population, intervention schedule, comparator, and endpoint layer would be required for the claim to survive a prospective test. This preserves the practical implication for readers: favorable signals can justify targeted follow-up, while unresolved tradeoffs still limit broad clinical or public-health recommendations.

Conclusion

The final interpretation is deliberately tiered. Blue Zones Diet Lifestyle has a biologically plausible geroscience rationale and selected clinical signals, but the corpus does not support treating mechanistic target engagement, intermediate biomarkers, and patient-relevant outcomes as interchangeable evidence.

The strongest interpretation is that positive signals in deficiency prevalence, longevity coexist with null signals in contextual adjacent evidence, longevity, mortality and survival and negative signals in contextual adjacent evidence. That profile supports further targeted research and careful hypothesis refinement, not unqualified clinical or public-health claims.

The current corpus may support blue zones diet lifestyle as a general health or lifestyle intervention where otherwise indicated, but does not justify marketing it as a standalone geroprotective or anti-aging intervention with proven hard-longevity effects. The safer translation path is a registered trial that specifies the endpoint layer in advance, pairs dosing with monitoring for metabolic and immune safety, and reports null or adverse signals with the same visibility as favorable results.

Additional corpus sources included animal/preclinical evidence; future work should prioritize studies that connect mechanistic studies (Fang 2021, Aiello 2021, Aliberti 2025) to direct clinical outcomes represented by the retained evidence base. Until that bridge is stronger, blue zones diet lifestyle remains a promising but bounded geroscience case whose most useful contribution is to define the next trial rather than to justify current clinical adoption.

The decisive unresolved question is not whether the intervention can move selected biomarkers or pathway markers, but whether those changes improve durable human function without offsetting harm, adherence failure, or loss in another clinically relevant domain. That question should set the bar for future claims, clinical translation, future study design, and any public recommendation.

What This Synthesis Adds

This synthesis maps 50 included sources on Blue zones diet lifestyle across 7 outcome classes and 528 cross-study disagreements. It separates endpoint-specific evidence from broad geroprotection claims so that favorable biomarker signals are not treated as proof of durable healthspan benefit.

Across 50 curated reference papers, the evidence base for Blue zones diet lifestyle shows a context-dependent profile. Positive signals appear in: deficiency prevalence, longevity. Negative signals appear in: contextual other. Null findings dominate: contextual other, longevity. The synthesis surfaces cross-study disagreements across outcome classes — see Cross-Domain Synthesis. The Blue zones diet lifestyle anti-aging case as currently constituted is incomplete: mechanistic plausibility coexists with mixed or sparse human-RCT evidence, and the boundary conditions remain to be established.

Prior reviews in the corpus (Lastoria 2023, Mazzola 2016) emphasize convergent signals on Blue zones diet lifestyle. This synthesis adds a design-level evidence-weighting layer and an explicit cross-study disagreement map, keeping boundary conditions visible instead of averaging them away in narrative summary.

Boundary-Condition Matrix

Outcome classDirect sourcesIndirect / mechanism sourcesDirection profileInterpretation boundary
longevity07null, positive, uncleardirect clinical gap
cardiometabolic01nulldirect clinical gap
frailty01nulldirect clinical gap
contextual adjacent evidence032mixed, negative, null, unclearconflict-resolution gap
mortality and survival06null, uncleardirect clinical gap
deficiency prevalence02positive, uncleardirect clinical gap
skeletal, fracture, and bone01uncleardirect clinical gap

Evidence-Gap Priority

PriorityGapRationale
P1longevity: direct clinical gap0 direct and 7 indirect sources; direction profile: null, positive, unclear
P2cardiometabolic: direct clinical gap0 direct and 1 indirect source; direction profile: null
P3frailty: direct clinical gap0 direct and 1 indirect source; direction profile: null
P4contextual adjacent evidence: conflict-resolution gap0 direct and 32 indirect sources; direction profile: mixed, negative, null, unclear
P5mortality and survival: direct clinical gap0 direct and 6 indirect sources; direction profile: null, unclear

Next-Study Design Recommendation

The next high-yield study for Blue zones diet lifestyle should target the longevity evidence gap, pre-register the primary endpoint, separate clinical from mechanistic endpoints, preserve safety and adherence capture, and include an analysis plan that can falsify the current boundary-condition claim rather than only confirming a favorable direction.

Structured Evidence Tables

The following tables present the structured evidence summary referenced throughout this paper. Numbers live in the tables; prose references them. Tables 1-3 cover included studies, per-study endpoint evidence, and cross-domain tensions; Table 4 is a supplemental design-level evidence weighting heuristic; Table 5 surfaces the underlying per-paper numeric index.

Table 1: Included Studies

CitationDesignTierNPopulationEndpointDirectionDirectnessTrial IDRepresentative p-valuen claims
Beker 2020ObservationalB2adultscontextual othernegativeindirectP < 0.001118
Yamamoto 2025ObservationalB2adultscardiometabolicnullindirectP < 0.00199
Evans 2014ObservationalB2adultsmortality survivalunclearindirectP < 0.00191
Pineiro-Fernandez 2025ObservationalB2adultsskeletal fracture boneunclearindirectP < 0.00178
Gimeno-Miguel 2019ObservationalB2adultscontextual othernullindirect76
Beker 2019ObservationalB2adultscontextual othernullindirectP = 0.13876
Murata 2023ObservationalB2adultscontextual othernullindirect71
Suh 2025ObservationalB2adultsmortality survivalnullindirectP < 0.00166
Wang 2019ObservationalB2adultsmortality survivalunclearindirectP < 0.00164
Hazra 2015ObservationalB2adultscontextual othernullindirectP < 0.00158
Biagi 2010ObservationalB2adultsdeficiency prevalencepositiveindirectP = 0.00157
Dai 2024ObservationalB2contextual othernullreview56
Garcia-Vivanco 2025ObservationalB2adultscontextual othernullindirectP = 0.0156
Cai 2016ObservationalB2adultscontextual othernullindirectP < 0.0555
Sebastiani 2021ObservationalB2adultscontextual othernullindirectP = 0.000352
Fang 2021Preclinical (animal/in vitro)C1mice (preclinical)contextual othernullmechanisticP < 0.00149
Lastoria 2023Review / meta-analysisB1longevityunclearreviewP < 0.00148
Jang 2023ObservationalB2adultslongevitynullindirectP = 0.03444
Gu 2015ObservationalB2frail / sarcopenic adultsmortality survivalunclearindirectP < 0.00141
Cai 2022ObservationalB2adultscontextual otherunclearindirectP < 0.0139
Lindberg 2025ObservationalB2adultsmortality survivalunclearindirect36
Sasaki 2023ObservationalB2adultsdeficiency prevalenceunclearindirect34
Arnold 2010ObservationalB2adultscontextual otherunclearindirectP < 0.00133
Vitale 2012ObservationalB2adultscontextual othernullindirectP < 0.00132
Feng 2022ObservationalB2adultscontextual othernullindirectP < 0.00132
MarcosPerez 2025ObservationalB2frail / sarcopenic adultsfrailtynullindirectP < 0.00131
Garagnani 2013ObservationalB2type 2 diabetes patientscontextual othernullindirect25
Collino 2013ObservationalB2adultscontextual othernullindirectP < 0.00122
Li 2023ObservationalB2adultscontextual othernullreviewP < 0.000122
Santos-Lozano 2020ObservationalB2adultscontextual othernullindirectP < 0.00120
Mandala 2023ObservationalB2contextual othermixedreviewP < 0.00120
Gavrilov 2011ObservationalB2adultscontextual othernullindirectP < 0.00119
Aiello 2021ObservationalB2adultscontextual othernullindirect19
Ruiz 2019ObservationalB2adultscontextual othernullindirectP < 0.00117
Marcon 2020ObservationalB2adultslongevitypositiveindirectP < 0.000117
Croize-Pourcelet 2022ObservationalB2adultscontextual othernullindirect13
Aliberti 2024ObservationalB2contextual otherunclearreview7
Ono 2024ObservationalB2adultscontextual othernullindirectP = 0.0047
Espinosa 2025ObservationalB2adultsmortality survivalnullindirect7
Najafi 2024ObservationalB2adultscontextual othernullindirect5
Aliberti 2025Preclinical (animal/in vitro)C1adultslongevitynullmechanistic5
Balistreri 2012ObservationalB2adultscontextual othernullindirect5
Wu 2019ObservationalB2adultscontextual othernullindirectP < 0.055
Ungvari 2023Preclinical (animal/in vitro)C1adultscontextual othernullmechanistic3
Aliberti 2025bObservationalB2contextual othernullindirect1
Aliberti 2025cObservationalB2adultslongevitynullindirect1
Govindaraju 2015ObservationalB2adultslongevitynullindirect1
Santoro 2017ObservationalB2adultscontextual othernullindirect1
Marston 2021ObservationalB2contextual othernullreview1
Mazzola 2016Review / meta-analysisB1adultslongevitynullreview1

Table 2: Per-Study Endpoint Evidence

Additional corpus sources included animal/preclinical evidence; | Endpoint | Study | p/CI | Direction | Directness | Tier | Interpretation | | --- | --- | --- | --- | --- | --- | --- | | contextual other | Beker 2020 | P < 0.001 | negative summary | indirect | B2 | reported statistic; source summary remains negative | | contextual other | Beker 2020 | P = 0.02 | negative summary | indirect | B2 | reported statistic; source summary remains negative | | contextual other | Beker 2020 | P = 0.57 | negative summary | indirect | B2 | reported statistic; source summary remains negative | | contextual other | Beker 2020 | P < 0.001 | negative summary | indirect | B2 | reported statistic; source summary remains negative | | contextual other | Beker 2020 | P = 0.004 | negative summary | indirect | B2 | reported statistic; source summary remains negative | | contextual other | Beker 2020 | P < 0.001 | negative summary | indirect | B2 | reported statistic; source summary remains negative | | cardiometabolic | Yamamoto 2025 | P = 0.014 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | cardiometabolic | Yamamoto 2025 | P = 0.005 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | cardiometabolic | Yamamoto 2025 | P < 0.001 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | cardiometabolic | Yamamoto 2025 | P = 0.009 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | mortality survival | Evans 2014 | P = 0.014 | unclear summary | indirect | B2 | reported statistic; source summary remains unclear | | mortality survival | Evans 2014 | P < 0.001 | unclear summary | indirect | B2 | reported statistic; source summary remains unclear | | mortality survival | Evans 2014 | P < 0.001 | unclear summary | indirect | B2 | reported statistic; source summary remains unclear | | mortality survival | Evans 2014 | P < 0.001 | unclear summary | indirect | B2 | reported statistic; source summary remains unclear | | skeletal fracture bone | Pineiro-Fernandez 2025 | P < 0.05 | unclear summary | indirect | B2 | reported statistic; source summary remains unclear | | skeletal fracture bone | Pineiro-Fernandez 2025 | P < 0.001 | unclear summary | indirect | B2 | reported statistic; source summary remains unclear | | skeletal fracture bone | Pineiro-Fernandez 2025 | P < 0.001 | unclear summary | indirect | B2 | reported statistic; source summary remains unclear | | skeletal fracture bone | Pineiro-Fernandez 2025 | P < 0.05 | unclear summary | indirect | B2 | reported statistic; source summary remains unclear | | skeletal fracture bone | Pineiro-Fernandez 2025 | P < 0.001 | unclear summary | indirect | B2 | reported statistic; source summary remains unclear | | skeletal fracture bone | Pineiro-Fernandez 2025 | P < 0.001 | unclear summary | indirect | B2 | reported statistic; source summary remains unclear | | contextual other | Gimeno-Miguel 2019 | — | null | indirect | B2 | no significant effect on contextual other | | contextual other | Beker 2019 | P = 0.809 | null summary | indirect | B2 | reported statistic; source summary remains null | | contextual other | Beker 2019 | P = 0.896 | null summary | indirect | B2 | reported statistic; source summary remains null | | contextual other | Beker 2019 | P = 0.877 | null summary | indirect | B2 | reported statistic; source summary remains null | | contextual other | Beker 2019 | P = 0.753 | null summary | indirect | B2 | reported statistic; source summary remains null | | contextual other | Beker 2019 | P = 0.623 | null summary | indirect | B2 | reported statistic; source summary remains null | | contextual other | Beker 2019 | P = 0.138 | null summary | indirect | B2 | reported statistic; source summary remains null | | contextual other | Murata 2023 | — | null | indirect | B2 | no significant effect on contextual other | | mortality survival | Suh 2025 | P = 0.785 | null summary | indirect | B2 | reported statistic; source summary remains null | | mortality survival | Suh 2025 | P < 0.001 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | mortality survival | Suh 2025 | P = 0.01 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | mortality survival | Suh 2025 | P < 0.001 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | mortality survival | Suh 2025 | P = 0.893 | null summary | indirect | B2 | reported statistic; source summary remains null | | mortality survival | Suh 2025 | P = 0.046 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | mortality survival | Wang 2019 | P < 0.001 | unclear summary | indirect | B2 | reported statistic; source summary remains unclear | | mortality survival | Wang 2019 | P = 0.257 | unclear summary | indirect | B2 | reported statistic; source summary remains unclear | | mortality survival | Wang 2019 | P = 0.016 | unclear summary | indirect | B2 | reported statistic; source summary remains unclear | | contextual other | Hazra 2015 | P < 0.001 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Hazra 2015 | P = 0.06 | null summary | indirect | B2 | reported statistic; source summary remains null | | contextual other | Hazra 2015 | P < 0.001 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Hazra 2015 | P < 0.001 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Hazra 2015 | P < 0.001 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Hazra 2015 | P = 0.06 | null summary | indirect | B2 | reported statistic; source summary remains null | | deficiency prevalence | Biagi 2010 | P = 0.001 | positive summary | indirect | B2 | reported statistic; source summary remains positive | | deficiency prevalence | Biagi 2010 | P = 0.02 | positive summary | indirect | B2 | reported statistic; source summary remains positive | | deficiency prevalence | Biagi 2010 | P = 0.002 | positive summary | indirect | B2 | reported statistic; source summary remains positive | | deficiency prevalence | Biagi 2010 | P = 0.05 | positive summary | indirect | B2 | reported statistic; source summary remains positive | | deficiency prevalence | Biagi 2010 | P = 0.05 | positive summary | indirect | B2 | reported statistic; source summary remains positive | | deficiency prevalence | Biagi 2010 | P = 0.03 | positive summary | indirect | B2 | reported statistic; source summary remains positive | | contextual other | Dai 2024 | — | null | review | B2 | no significant effect on contextual other | | contextual other | Garcia-Vivanco 2025 | P = 0.01 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Garcia-Vivanco 2025 | P = 0.02 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Garcia-Vivanco 2025 | P = 0.02 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Garcia-Vivanco 2025 | P = 0.026 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Garcia-Vivanco 2025 | P = 0.026 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Garcia-Vivanco 2025 | P = 0.02 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Cai 2016 | P < 0.05 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Cai 2016 | P > 0.05 | null summary | indirect | B2 | reported statistic; source summary remains null | | contextual other | Cai 2016 | P > 0.05 | null summary | indirect | B2 | reported statistic; source summary remains null | | contextual other | Cai 2016 | P < 0.05 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Cai 2016 | P < 0.05 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Cai 2016 | P < 0.05 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Sebastiani 2021 | P < 0.05 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Sebastiani 2021 | P = 0.0003 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Sebastiani 2021 | P = 0.0003 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Sebastiani 2021 | P = 0.009 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Sebastiani 2021 | P = 0.02 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Sebastiani 2021 | P > 0.2 | null summary | indirect | B2 | reported statistic; source summary remains null | | contextual other | Fang 2021 | P < 0.001 | significant statistic | mechanistic | C1 | significant statistic; source-level direction remains null | | contextual other | Fang 2021 | P < 0.05 | significant statistic | mechanistic | C1 | significant statistic; source-level direction remains null | | contextual other | Fang 2021 | P < 0.05 | significant statistic | mechanistic | C1 | significant statistic; source-level direction remains null | | contextual other | Fang 2021 | P < 0.05 | significant statistic | mechanistic | C1 | significant statistic; source-level direction remains null | | contextual other | Fang 2021 | P < 0.05 | significant statistic | mechanistic | C1 | significant statistic; source-level direction remains null | | contextual other | Fang 2021 | P < 0.05 | significant statistic | mechanistic | C1 | significant statistic; source-level direction remains null | | longevity | Lastoria 2023 | P < 0.001 | unclear summary | review | B1 | reported statistic; source summary remains unclear | | longevity | Lastoria 2023 | P < 0.001 | unclear summary | review | B1 | reported statistic; source summary remains unclear | | longevity | Lastoria 2023 | P = 0.034 | unclear summary | review | B1 | reported statistic; source summary remains unclear | | longevity | Jang 2023 | P = 0.034 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | longevity | Jang 2023 | P = 0.034 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | longevity | Jang 2023 | P = 0.254 | null summary | indirect | B2 | reported statistic; source summary remains null | | mortality survival | Gu 2015 | P < 0.05 | unclear summary | indirect | B2 | reported statistic; source summary remains unclear | | mortality survival | Gu 2015 | P < 0.1 | unclear summary | indirect | B2 | reported statistic; source summary remains unclear | | mortality survival | Gu 2015 | P < 0.05 | unclear summary | indirect | B2 | reported statistic; source summary remains unclear | | mortality survival | Gu 2015 | P < 0.01 | unclear summary | indirect | B2 | reported statistic; source summary remains unclear | | mortality survival | Gu 2015 | P < 0.001 | unclear summary | indirect | B2 | reported statistic; source summary remains unclear | | mortality survival | Gu 2015 | P < 0.1 | unclear summary | indirect | B2 | reported statistic; source summary remains unclear | | contextual other | Cai 2022 | P < 0.05 | unclear summary | indirect | B2 | reported statistic; source summary remains unclear | | contextual other | Cai 2022 | P < 0.01 | unclear summary | indirect | B2 | reported statistic; source summary remains unclear | | contextual other | Cai 2022 | P > 0.05 | unclear summary | indirect | B2 | reported statistic; source summary remains unclear | | contextual other | Cai 2022 | P < 0.05 | unclear summary | indirect | B2 | reported statistic; source summary remains unclear | | contextual other | Cai 2022 | P < 0.05 | unclear summary | indirect | B2 | reported statistic; source summary remains unclear | | contextual other | Cai 2022 | P < 0.05 | unclear summary | indirect | B2 | reported statistic; source summary remains unclear | | mortality survival | Lindberg 2025 | — | unclear | indirect | B2 | unclear effect on mortality survival | | deficiency prevalence | Sasaki 2023 | — | unclear | indirect | B2 | unclear effect on deficiency prevalence | | contextual other | Arnold 2010 | P < 0.001 | unclear summary | indirect | B2 | reported statistic; source summary remains unclear | | contextual other | Arnold 2010 | P < 0.005 | unclear summary | indirect | B2 | reported statistic; source summary remains unclear | | contextual other | Vitale 2012 | P < 0.01 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Vitale 2012 | P < 0.01 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Vitale 2012 | P < 0.001 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Vitale 2012 | P < 0.001 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Vitale 2012 | P = 0.006 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Vitale 2012 | P = 0.06 | null summary | indirect | B2 | reported statistic; source summary remains null | | contextual other | Feng 2022 | P < 0.05 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Feng 2022 | P < 0.05 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Feng 2022 | P < 0.001 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Feng 2022 | P < 0.001 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Feng 2022 | P < 0.001 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Feng 2022 | P < 0.001 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | frailty | MarcosPerez 2025 | P = 0.01 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | frailty | MarcosPerez 2025 | P < 0.001 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | frailty | MarcosPerez 2025 | P = 0.001 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | frailty | MarcosPerez 2025 | P = 0.05 | null summary | indirect | B2 | reported statistic; source summary remains null | | frailty | MarcosPerez 2025 | P < 0.001 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | frailty | MarcosPerez 2025 | P < 0.001 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Garagnani 2013 | — | null | indirect | B2 | no significant effect on contextual other | | contextual other | Collino 2013 | P < 0.001 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Collino 2013 | P < 0.001 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Collino 2013 | P < 0.01 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Collino 2013 | P < 0.05 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Collino 2013 | P < 0.01 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Collino 2013 | P < 0.01 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Li 2023 | P < 0.0001 | significant statistic | review | B2 | significant statistic; source-level direction remains null | | contextual other | Li 2023 | P = 0.03 | significant statistic | review | B2 | significant statistic; source-level direction remains null | | contextual other | Li 2023 | P = 0.01 | significant statistic | review | B2 | significant statistic; source-level direction remains null | | contextual other | Li 2023 | P < 0.0001 | significant statistic | review | B2 | significant statistic; source-level direction remains null | | contextual other | Santos-Lozano 2020 | P < 0.001 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Mandala 2023 | P < 0.001 | mixed summary | review | B2 | reported statistic; source summary remains mixed | | contextual other | Mandala 2023 | P < 0.001 | mixed summary | review | B2 | reported statistic; source summary remains mixed | | contextual other | Mandala 2023 | P < 0.001 | mixed summary | review | B2 | reported statistic; source summary remains mixed | | contextual other | Gavrilov 2011 | P < 0.001 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Gavrilov 2011 | P = 0.025 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Gavrilov 2011 | P = 0.045 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Gavrilov 2011 | P = 0.053 | null summary | indirect | B2 | reported statistic; source summary remains null | | contextual other | Aiello 2021 | — | null | indirect | B2 | no significant effect on contextual other | | contextual other | Ruiz 2019 | P < 0.001 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Ruiz 2019 | P = 0.03 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Ruiz 2019 | P < 0.001 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Ruiz 2019 | P < 0.001 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Ruiz 2019 | P < 0.001 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Ruiz 2019 | P = 0.003 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | longevity | Marcon 2020 | P < 0.0001 | positive summary | indirect | B2 | reported statistic; source summary remains positive | | contextual other | Croize-Pourcelet 2022 | — | null | indirect | B2 | no significant effect on contextual other | | contextual other | Aliberti 2024 | — | unclear | review | B2 | unclear effect on contextual other | | contextual other | Ono 2024 | P = 0.004 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | mortality survival | Espinosa 2025 | — | null | indirect | B2 | no significant effect on mortality survival | | contextual other | Najafi 2024 | — | null | indirect | B2 | no significant effect on contextual other | | longevity | Aliberti 2025 | — | null | mechanistic | C1 | no significant effect on longevity | | contextual other | Balistreri 2012 | — | null | indirect | B2 | no significant effect on contextual other | | contextual other | Wu 2019 | P < 0.05 | significant statistic | indirect | B2 | significant statistic; source-level direction remains null | | contextual other | Ungvari 2023 | — | null | mechanistic | C1 | no significant effect on contextual other | | contextual other | Aliberti 2025b | — | null | indirect | B2 | no significant effect on contextual other | | longevity | Aliberti 2025c | — | null | indirect | B2 | no significant effect on longevity | | longevity | Govindaraju 2015 | — | null | indirect | B2 | no significant effect on longevity | | contextual other | Santoro 2017 | — | null | indirect | B2 | no significant effect on contextual other | | contextual other | Marston 2021 | — | null | review | B2 | no significant effect on contextual other | | longevity | Mazzola 2016 | — | null | review | B1 | no significant effect on longevity |

Table 3: Cross-Domain Tensions

Additional corpus sources included animal/preclinical evidence; | Tension kind | Severity | source A | source B | Outcome class | Summary | Practical implication | | --- | --- | --- | --- | --- | --- | --- | | agreement | 1 | Ungvari 2023 | Murata 2023 | contextual other | Ungvari 2023 (null) vs Murata 2023 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Ungvari 2023 | Aliberti 2024 | contextual other | Ungvari 2023 (null) vs Aliberti 2024 (unclear) on contextual other | null vs positive (notable) | | agreement | 1 | Ungvari 2023 | Najafi 2024 | contextual other | Ungvari 2023 (null) vs Najafi 2024 (null) on contextual other | agreement (minor) | | agreement | 1 | Ungvari 2023 | Ono 2024 | contextual other | Ungvari 2023 (null) vs Ono 2024 (null) on contextual other | agreement (minor) | | agreement | 1 | Ungvari 2023 | Dai 2024 | contextual other | Ungvari 2023 (null) vs Dai 2024 (null) on contextual other | agreement (minor) | | agreement | 1 | Ungvari 2023 | Aliberti 2025b | contextual other | Ungvari 2023 (null) vs Aliberti 2025b (null) on contextual other | agreement (minor) | | agreement | 1 | Ungvari 2023 | Garcia-Vivanco 2025 | contextual other | Ungvari 2023 (null) vs Garcia-Vivanco 2025 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Ungvari 2023 | Arnold 2010 | contextual other | Ungvari 2023 (null) vs Arnold 2010 (unclear) on contextual other | null vs positive (notable) | | agreement | 1 | Ungvari 2023 | Gavrilov 2011 | contextual other | Ungvari 2023 (null) vs Gavrilov 2011 (null) on contextual other | agreement (minor) | | agreement | 1 | Ungvari 2023 | Balistreri 2012 | contextual other | Ungvari 2023 (null) vs Balistreri 2012 (null) on contextual other | agreement (minor) | | agreement | 1 | Ungvari 2023 | Vitale 2012 | contextual other | Ungvari 2023 (null) vs Vitale 2012 (null) on contextual other | agreement (minor) | | agreement | 1 | Ungvari 2023 | Collino 2013 | contextual other | Ungvari 2023 (null) vs Collino 2013 (null) on contextual other | agreement (minor) | | agreement | 1 | Ungvari 2023 | Garagnani 2013 | contextual other | Ungvari 2023 (null) vs Garagnani 2013 (null) on contextual other | agreement (minor) | | agreement | 1 | Ungvari 2023 | Hazra 2015 | contextual other | Ungvari 2023 (null) vs Hazra 2015 (null) on contextual other | agreement (minor) | | agreement | 1 | Ungvari 2023 | Cai 2016 | contextual other | Ungvari 2023 (null) vs Cai 2016 (null) on contextual other | agreement (minor) | | agreement | 1 | Ungvari 2023 | Santoro 2017 | contextual other | Ungvari 2023 (null) vs Santoro 2017 (null) on contextual other | agreement (minor) | | agreement | 1 | Ungvari 2023 | Wu 2019 | contextual other | Ungvari 2023 (null) vs Wu 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Ungvari 2023 | Gimeno-Miguel 2019 | contextual other | Ungvari 2023 (null) vs Gimeno-Miguel 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Ungvari 2023 | Ruiz 2019 | contextual other | Ungvari 2023 (null) vs Ruiz 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Ungvari 2023 | Beker 2019 | contextual other | Ungvari 2023 (null) vs Beker 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Ungvari 2023 | Santos-Lozano 2020 | contextual other | Ungvari 2023 (null) vs Santos-Lozano 2020 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Ungvari 2023 | Beker 2020 | contextual other | Ungvari 2023 (null) vs Beker 2020 (negative) on contextual other | null vs positive (notable) | | agreement | 1 | Ungvari 2023 | Marston 2021 | contextual other | Ungvari 2023 (null) vs Marston 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Ungvari 2023 | Sebastiani 2021 | contextual other | Ungvari 2023 (null) vs Sebastiani 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Ungvari 2023 | Aiello 2021 | contextual other | Ungvari 2023 (null) vs Aiello 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Ungvari 2023 | Fang 2021 | contextual other | Ungvari 2023 (null) vs Fang 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Ungvari 2023 | Feng 2022 | contextual other | Ungvari 2023 (null) vs Feng 2022 (null) on contextual other | agreement (minor) | | agreement | 1 | Ungvari 2023 | Croize-Pourcelet 2022 | contextual other | Ungvari 2023 (null) vs Croize-Pourcelet 2022 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Ungvari 2023 | Cai 2022 | contextual other | Ungvari 2023 (null) vs Cai 2022 (unclear) on contextual other | null vs positive (notable) | | disagreement | 4 | Ungvari 2023 | Mandala 2023 | contextual other | Ungvari 2023 (null) vs Mandala 2023 (mixed) on contextual other | disagreement (load-bearing) | | agreement | 1 | Ungvari 2023 | Li 2023 | contextual other | Ungvari 2023 (null) vs Li 2023 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Jang 2023 | Lastoria 2023 | longevity | Jang 2023 (null) vs Lastoria 2023 (unclear) on longevity | null vs positive (notable) | | agreement | 1 | Jang 2023 | Aliberti 2025c | longevity | Jang 2023 (null) vs Aliberti 2025c (null) on longevity | agreement (minor) | | agreement | 1 | Jang 2023 | Aliberti 2025 | longevity | Jang 2023 (null) vs Aliberti 2025 (null) on longevity | agreement (minor) | | agreement | 1 | Jang 2023 | Govindaraju 2015 | longevity | Jang 2023 (null) vs Govindaraju 2015 (null) on longevity | agreement (minor) | | null vs positive | 3 | Jang 2023 | Marcon 2020 | longevity | Jang 2023 (null) vs Marcon 2020 (positive) on longevity | null vs positive (notable) | | agreement | 1 | Jang 2023 | Mazzola 2016 | longevity | Jang 2023 (null) vs Mazzola 2016 (null) on longevity | agreement (minor) | | null vs positive | 3 | Lastoria 2023 | Aliberti 2025c | longevity | Lastoria 2023 (unclear) vs Aliberti 2025c (null) on longevity | null vs positive (notable) | | null vs positive | 3 | Lastoria 2023 | Aliberti 2025 | longevity | Lastoria 2023 (unclear) vs Aliberti 2025 (null) on longevity | null vs positive (notable) | | null vs positive | 3 | Lastoria 2023 | Govindaraju 2015 | longevity | Lastoria 2023 (unclear) vs Govindaraju 2015 (null) on longevity | null vs positive (notable) | | null vs positive | 3 | Lastoria 2023 | Mazzola 2016 | longevity | Lastoria 2023 (unclear) vs Mazzola 2016 (null) on longevity | null vs positive (notable) | | null vs positive | 3 | Murata 2023 | Aliberti 2024 | contextual other | Murata 2023 (null) vs Aliberti 2024 (unclear) on contextual other | null vs positive (notable) | | agreement | 1 | Murata 2023 | Najafi 2024 | contextual other | Murata 2023 (null) vs Najafi 2024 (null) on contextual other | agreement (minor) | | agreement | 1 | Murata 2023 | Ono 2024 | contextual other | Murata 2023 (null) vs Ono 2024 (null) on contextual other | agreement (minor) | | agreement | 1 | Murata 2023 | Dai 2024 | contextual other | Murata 2023 (null) vs Dai 2024 (null) on contextual other | agreement (minor) | | agreement | 1 | Murata 2023 | Aliberti 2025b | contextual other | Murata 2023 (null) vs Aliberti 2025b (null) on contextual other | agreement (minor) | | agreement | 1 | Murata 2023 | Garcia-Vivanco 2025 | contextual other | Murata 2023 (null) vs Garcia-Vivanco 2025 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Murata 2023 | Arnold 2010 | contextual other | Murata 2023 (null) vs Arnold 2010 (unclear) on contextual other | null vs positive (notable) | | agreement | 1 | Murata 2023 | Gavrilov 2011 | contextual other | Murata 2023 (null) vs Gavrilov 2011 (null) on contextual other | agreement (minor) | | agreement | 1 | Murata 2023 | Balistreri 2012 | contextual other | Murata 2023 (null) vs Balistreri 2012 (null) on contextual other | agreement (minor) | | agreement | 1 | Murata 2023 | Vitale 2012 | contextual other | Murata 2023 (null) vs Vitale 2012 (null) on contextual other | agreement (minor) | | agreement | 1 | Murata 2023 | Collino 2013 | contextual other | Murata 2023 (null) vs Collino 2013 (null) on contextual other | agreement (minor) | | agreement | 1 | Murata 2023 | Garagnani 2013 | contextual other | Murata 2023 (null) vs Garagnani 2013 (null) on contextual other | agreement (minor) | | agreement | 1 | Murata 2023 | Hazra 2015 | contextual other | Murata 2023 (null) vs Hazra 2015 (null) on contextual other | agreement (minor) | | agreement | 1 | Murata 2023 | Cai 2016 | contextual other | Murata 2023 (null) vs Cai 2016 (null) on contextual other | agreement (minor) | | agreement | 1 | Murata 2023 | Santoro 2017 | contextual other | Murata 2023 (null) vs Santoro 2017 (null) on contextual other | agreement (minor) | | agreement | 1 | Murata 2023 | Wu 2019 | contextual other | Murata 2023 (null) vs Wu 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Murata 2023 | Gimeno-Miguel 2019 | contextual other | Murata 2023 (null) vs Gimeno-Miguel 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Murata 2023 | Ruiz 2019 | contextual other | Murata 2023 (null) vs Ruiz 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Murata 2023 | Beker 2019 | contextual other | Murata 2023 (null) vs Beker 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Murata 2023 | Santos-Lozano 2020 | contextual other | Murata 2023 (null) vs Santos-Lozano 2020 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Murata 2023 | Beker 2020 | contextual other | Murata 2023 (null) vs Beker 2020 (negative) on contextual other | null vs positive (notable) | | agreement | 1 | Murata 2023 | Marston 2021 | contextual other | Murata 2023 (null) vs Marston 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Murata 2023 | Sebastiani 2021 | contextual other | Murata 2023 (null) vs Sebastiani 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Murata 2023 | Aiello 2021 | contextual other | Murata 2023 (null) vs Aiello 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Murata 2023 | Fang 2021 | contextual other | Murata 2023 (null) vs Fang 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Murata 2023 | Feng 2022 | contextual other | Murata 2023 (null) vs Feng 2022 (null) on contextual other | agreement (minor) | | agreement | 1 | Murata 2023 | Croize-Pourcelet 2022 | contextual other | Murata 2023 (null) vs Croize-Pourcelet 2022 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Murata 2023 | Cai 2022 | contextual other | Murata 2023 (null) vs Cai 2022 (unclear) on contextual other | null vs positive (notable) | | disagreement | 4 | Murata 2023 | Mandala 2023 | contextual other | Murata 2023 (null) vs Mandala 2023 (mixed) on contextual other | disagreement (load-bearing) | | agreement | 1 | Murata 2023 | Li 2023 | contextual other | Murata 2023 (null) vs Li 2023 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Aliberti 2024 | Najafi 2024 | contextual other | Aliberti 2024 (unclear) vs Najafi 2024 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Aliberti 2024 | Ono 2024 | contextual other | Aliberti 2024 (unclear) vs Ono 2024 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Aliberti 2024 | Dai 2024 | contextual other | Aliberti 2024 (unclear) vs Dai 2024 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Aliberti 2024 | Aliberti 2025b | contextual other | Aliberti 2024 (unclear) vs Aliberti 2025b (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Aliberti 2024 | Garcia-Vivanco 2025 | contextual other | Aliberti 2024 (unclear) vs Garcia-Vivanco 2025 (null) on contextual other | null vs positive (notable) | | agreement | 1 | Aliberti 2024 | Arnold 2010 | contextual other | Aliberti 2024 (unclear) vs Arnold 2010 (unclear) on contextual other | agreement (minor) | | null vs positive | 3 | Aliberti 2024 | Gavrilov 2011 | contextual other | Aliberti 2024 (unclear) vs Gavrilov 2011 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Aliberti 2024 | Balistreri 2012 | contextual other | Aliberti 2024 (unclear) vs Balistreri 2012 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Aliberti 2024 | Vitale 2012 | contextual other | Aliberti 2024 (unclear) vs Vitale 2012 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Aliberti 2024 | Collino 2013 | contextual other | Aliberti 2024 (unclear) vs Collino 2013 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Aliberti 2024 | Garagnani 2013 | contextual other | Aliberti 2024 (unclear) vs Garagnani 2013 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Aliberti 2024 | Hazra 2015 | contextual other | Aliberti 2024 (unclear) vs Hazra 2015 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Aliberti 2024 | Cai 2016 | contextual other | Aliberti 2024 (unclear) vs Cai 2016 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Aliberti 2024 | Santoro 2017 | contextual other | Aliberti 2024 (unclear) vs Santoro 2017 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Aliberti 2024 | Wu 2019 | contextual other | Aliberti 2024 (unclear) vs Wu 2019 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Aliberti 2024 | Gimeno-Miguel 2019 | contextual other | Aliberti 2024 (unclear) vs Gimeno-Miguel 2019 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Aliberti 2024 | Ruiz 2019 | contextual other | Aliberti 2024 (unclear) vs Ruiz 2019 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Aliberti 2024 | Beker 2019 | contextual other | Aliberti 2024 (unclear) vs Beker 2019 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Aliberti 2024 | Santos-Lozano 2020 | contextual other | Aliberti 2024 (unclear) vs Santos-Lozano 2020 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Aliberti 2024 | Marston 2021 | contextual other | Aliberti 2024 (unclear) vs Marston 2021 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Aliberti 2024 | Sebastiani 2021 | contextual other | Aliberti 2024 (unclear) vs Sebastiani 2021 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Aliberti 2024 | Aiello 2021 | contextual other | Aliberti 2024 (unclear) vs Aiello 2021 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Aliberti 2024 | Fang 2021 | contextual other | Aliberti 2024 (unclear) vs Fang 2021 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Aliberti 2024 | Feng 2022 | contextual other | Aliberti 2024 (unclear) vs Feng 2022 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Aliberti 2024 | Croize-Pourcelet 2022 | contextual other | Aliberti 2024 (unclear) vs Croize-Pourcelet 2022 (null) on contextual other | null vs positive (notable) | | agreement | 1 | Aliberti 2024 | Cai 2022 | contextual other | Aliberti 2024 (unclear) vs Cai 2022 (unclear) on contextual other | agreement (minor) | | disagreement | 4 | Aliberti 2024 | Mandala 2023 | contextual other | Aliberti 2024 (unclear) vs Mandala 2023 (mixed) on contextual other | disagreement (load-bearing) | | null vs positive | 3 | Aliberti 2024 | Li 2023 | contextual other | Aliberti 2024 (unclear) vs Li 2023 (null) on contextual other | null vs positive (notable) | | agreement | 1 | Najafi 2024 | Ono 2024 | contextual other | Najafi 2024 (null) vs Ono 2024 (null) on contextual other | agreement (minor) | | agreement | 1 | Najafi 2024 | Dai 2024 | contextual other | Najafi 2024 (null) vs Dai 2024 (null) on contextual other | agreement (minor) | | agreement | 1 | Najafi 2024 | Aliberti 2025b | contextual other | Najafi 2024 (null) vs Aliberti 2025b (null) on contextual other | agreement (minor) | | agreement | 1 | Najafi 2024 | Garcia-Vivanco 2025 | contextual other | Najafi 2024 (null) vs Garcia-Vivanco 2025 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Najafi 2024 | Arnold 2010 | contextual other | Najafi 2024 (null) vs Arnold 2010 (unclear) on contextual other | null vs positive (notable) | | agreement | 1 | Najafi 2024 | Gavrilov 2011 | contextual other | Najafi 2024 (null) vs Gavrilov 2011 (null) on contextual other | agreement (minor) | | agreement | 1 | Najafi 2024 | Balistreri 2012 | contextual other | Najafi 2024 (null) vs Balistreri 2012 (null) on contextual other | agreement (minor) | | agreement | 1 | Najafi 2024 | Vitale 2012 | contextual other | Najafi 2024 (null) vs Vitale 2012 (null) on contextual other | agreement (minor) | | agreement | 1 | Najafi 2024 | Collino 2013 | contextual other | Najafi 2024 (null) vs Collino 2013 (null) on contextual other | agreement (minor) | | agreement | 1 | Najafi 2024 | Garagnani 2013 | contextual other | Najafi 2024 (null) vs Garagnani 2013 (null) on contextual other | agreement (minor) | | agreement | 1 | Najafi 2024 | Hazra 2015 | contextual other | Najafi 2024 (null) vs Hazra 2015 (null) on contextual other | agreement (minor) | | agreement | 1 | Najafi 2024 | Cai 2016 | contextual other | Najafi 2024 (null) vs Cai 2016 (null) on contextual other | agreement (minor) | | agreement | 1 | Najafi 2024 | Santoro 2017 | contextual other | Najafi 2024 (null) vs Santoro 2017 (null) on contextual other | agreement (minor) | | agreement | 1 | Najafi 2024 | Wu 2019 | contextual other | Najafi 2024 (null) vs Wu 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Najafi 2024 | Gimeno-Miguel 2019 | contextual other | Najafi 2024 (null) vs Gimeno-Miguel 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Najafi 2024 | Ruiz 2019 | contextual other | Najafi 2024 (null) vs Ruiz 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Najafi 2024 | Beker 2019 | contextual other | Najafi 2024 (null) vs Beker 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Najafi 2024 | Santos-Lozano 2020 | contextual other | Najafi 2024 (null) vs Santos-Lozano 2020 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Najafi 2024 | Beker 2020 | contextual other | Najafi 2024 (null) vs Beker 2020 (negative) on contextual other | null vs positive (notable) | | agreement | 1 | Najafi 2024 | Marston 2021 | contextual other | Najafi 2024 (null) vs Marston 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Najafi 2024 | Sebastiani 2021 | contextual other | Najafi 2024 (null) vs Sebastiani 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Najafi 2024 | Aiello 2021 | contextual other | Najafi 2024 (null) vs Aiello 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Najafi 2024 | Fang 2021 | contextual other | Najafi 2024 (null) vs Fang 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Najafi 2024 | Feng 2022 | contextual other | Najafi 2024 (null) vs Feng 2022 (null) on contextual other | agreement (minor) | | agreement | 1 | Najafi 2024 | Croize-Pourcelet 2022 | contextual other | Najafi 2024 (null) vs Croize-Pourcelet 2022 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Najafi 2024 | Cai 2022 | contextual other | Najafi 2024 (null) vs Cai 2022 (unclear) on contextual other | null vs positive (notable) | | disagreement | 4 | Najafi 2024 | Mandala 2023 | contextual other | Najafi 2024 (null) vs Mandala 2023 (mixed) on contextual other | disagreement (load-bearing) | | agreement | 1 | Najafi 2024 | Li 2023 | contextual other | Najafi 2024 (null) vs Li 2023 (null) on contextual other | agreement (minor) | | agreement | 1 | Ono 2024 | Dai 2024 | contextual other | Ono 2024 (null) vs Dai 2024 (null) on contextual other | agreement (minor) | | agreement | 1 | Ono 2024 | Aliberti 2025b | contextual other | Ono 2024 (null) vs Aliberti 2025b (null) on contextual other | agreement (minor) | | agreement | 1 | Ono 2024 | Garcia-Vivanco 2025 | contextual other | Ono 2024 (null) vs Garcia-Vivanco 2025 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Ono 2024 | Arnold 2010 | contextual other | Ono 2024 (null) vs Arnold 2010 (unclear) on contextual other | null vs positive (notable) | | agreement | 1 | Ono 2024 | Gavrilov 2011 | contextual other | Ono 2024 (null) vs Gavrilov 2011 (null) on contextual other | agreement (minor) | | agreement | 1 | Ono 2024 | Balistreri 2012 | contextual other | Ono 2024 (null) vs Balistreri 2012 (null) on contextual other | agreement (minor) | | agreement | 1 | Ono 2024 | Vitale 2012 | contextual other | Ono 2024 (null) vs Vitale 2012 (null) on contextual other | agreement (minor) | | agreement | 1 | Ono 2024 | Collino 2013 | contextual other | Ono 2024 (null) vs Collino 2013 (null) on contextual other | agreement (minor) | | agreement | 1 | Ono 2024 | Garagnani 2013 | contextual other | Ono 2024 (null) vs Garagnani 2013 (null) on contextual other | agreement (minor) | | agreement | 1 | Ono 2024 | Hazra 2015 | contextual other | Ono 2024 (null) vs Hazra 2015 (null) on contextual other | agreement (minor) | | agreement | 1 | Ono 2024 | Cai 2016 | contextual other | Ono 2024 (null) vs Cai 2016 (null) on contextual other | agreement (minor) | | agreement | 1 | Ono 2024 | Santoro 2017 | contextual other | Ono 2024 (null) vs Santoro 2017 (null) on contextual other | agreement (minor) | | agreement | 1 | Ono 2024 | Wu 2019 | contextual other | Ono 2024 (null) vs Wu 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Ono 2024 | Gimeno-Miguel 2019 | contextual other | Ono 2024 (null) vs Gimeno-Miguel 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Ono 2024 | Ruiz 2019 | contextual other | Ono 2024 (null) vs Ruiz 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Ono 2024 | Beker 2019 | contextual other | Ono 2024 (null) vs Beker 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Ono 2024 | Santos-Lozano 2020 | contextual other | Ono 2024 (null) vs Santos-Lozano 2020 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Ono 2024 | Beker 2020 | contextual other | Ono 2024 (null) vs Beker 2020 (negative) on contextual other | null vs positive (notable) | | agreement | 1 | Ono 2024 | Marston 2021 | contextual other | Ono 2024 (null) vs Marston 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Ono 2024 | Sebastiani 2021 | contextual other | Ono 2024 (null) vs Sebastiani 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Ono 2024 | Aiello 2021 | contextual other | Ono 2024 (null) vs Aiello 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Ono 2024 | Fang 2021 | contextual other | Ono 2024 (null) vs Fang 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Ono 2024 | Feng 2022 | contextual other | Ono 2024 (null) vs Feng 2022 (null) on contextual other | agreement (minor) | | agreement | 1 | Ono 2024 | Croize-Pourcelet 2022 | contextual other | Ono 2024 (null) vs Croize-Pourcelet 2022 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Ono 2024 | Cai 2022 | contextual other | Ono 2024 (null) vs Cai 2022 (unclear) on contextual other | null vs positive (notable) | | disagreement | 4 | Ono 2024 | Mandala 2023 | contextual other | Ono 2024 (null) vs Mandala 2023 (mixed) on contextual other | disagreement (load-bearing) | | agreement | 1 | Ono 2024 | Li 2023 | contextual other | Ono 2024 (null) vs Li 2023 (null) on contextual other | agreement (minor) | | agreement | 1 | Dai 2024 | Aliberti 2025b | contextual other | Dai 2024 (null) vs Aliberti 2025b (null) on contextual other | agreement (minor) | | agreement | 1 | Dai 2024 | Garcia-Vivanco 2025 | contextual other | Dai 2024 (null) vs Garcia-Vivanco 2025 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Dai 2024 | Arnold 2010 | contextual other | Dai 2024 (null) vs Arnold 2010 (unclear) on contextual other | null vs positive (notable) | | agreement | 1 | Dai 2024 | Gavrilov 2011 | contextual other | Dai 2024 (null) vs Gavrilov 2011 (null) on contextual other | agreement (minor) | | agreement | 1 | Dai 2024 | Balistreri 2012 | contextual other | Dai 2024 (null) vs Balistreri 2012 (null) on contextual other | agreement (minor) | | agreement | 1 | Dai 2024 | Vitale 2012 | contextual other | Dai 2024 (null) vs Vitale 2012 (null) on contextual other | agreement (minor) | | agreement | 1 | Dai 2024 | Collino 2013 | contextual other | Dai 2024 (null) vs Collino 2013 (null) on contextual other | agreement (minor) | | agreement | 1 | Dai 2024 | Garagnani 2013 | contextual other | Dai 2024 (null) vs Garagnani 2013 (null) on contextual other | agreement (minor) | | agreement | 1 | Dai 2024 | Hazra 2015 | contextual other | Dai 2024 (null) vs Hazra 2015 (null) on contextual other | agreement (minor) | | agreement | 1 | Dai 2024 | Cai 2016 | contextual other | Dai 2024 (null) vs Cai 2016 (null) on contextual other | agreement (minor) | | agreement | 1 | Dai 2024 | Santoro 2017 | contextual other | Dai 2024 (null) vs Santoro 2017 (null) on contextual other | agreement (minor) | | agreement | 1 | Dai 2024 | Wu 2019 | contextual other | Dai 2024 (null) vs Wu 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Dai 2024 | Gimeno-Miguel 2019 | contextual other | Dai 2024 (null) vs Gimeno-Miguel 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Dai 2024 | Ruiz 2019 | contextual other | Dai 2024 (null) vs Ruiz 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Dai 2024 | Beker 2019 | contextual other | Dai 2024 (null) vs Beker 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Dai 2024 | Santos-Lozano 2020 | contextual other | Dai 2024 (null) vs Santos-Lozano 2020 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Dai 2024 | Beker 2020 | contextual other | Dai 2024 (null) vs Beker 2020 (negative) on contextual other | null vs positive (notable) | | agreement | 1 | Dai 2024 | Marston 2021 | contextual other | Dai 2024 (null) vs Marston 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Dai 2024 | Sebastiani 2021 | contextual other | Dai 2024 (null) vs Sebastiani 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Dai 2024 | Aiello 2021 | contextual other | Dai 2024 (null) vs Aiello 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Dai 2024 | Fang 2021 | contextual other | Dai 2024 (null) vs Fang 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Dai 2024 | Feng 2022 | contextual other | Dai 2024 (null) vs Feng 2022 (null) on contextual other | agreement (minor) | | agreement | 1 | Dai 2024 | Croize-Pourcelet 2022 | contextual other | Dai 2024 (null) vs Croize-Pourcelet 2022 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Dai 2024 | Cai 2022 | contextual other | Dai 2024 (null) vs Cai 2022 (unclear) on contextual other | null vs positive (notable) | | disagreement | 4 | Dai 2024 | Mandala 2023 | contextual other | Dai 2024 (null) vs Mandala 2023 (mixed) on contextual other | disagreement (load-bearing) | | agreement | 1 | Dai 2024 | Li 2023 | contextual other | Dai 2024 (null) vs Li 2023 (null) on contextual other | agreement (minor) | | agreement | 1 | Espinosa 2025 | Suh 2025 | mortality survival | Espinosa 2025 (null) vs Suh 2025 (null) on mortality survival | agreement (minor) | | null vs positive | 3 | Espinosa 2025 | Lindberg 2025 | mortality survival | Espinosa 2025 (null) vs Lindberg 2025 (unclear) on mortality survival | null vs positive (notable) | | null vs positive | 3 | Espinosa 2025 | Evans 2014 | mortality survival | Espinosa 2025 (null) vs Evans 2014 (unclear) on mortality survival | null vs positive (notable) | | null vs positive | 3 | Espinosa 2025 | Gu 2015 | mortality survival | Espinosa 2025 (null) vs Gu 2015 (unclear) on mortality survival | null vs positive (notable) | | null vs positive | 3 | Espinosa 2025 | Wang 2019 | mortality survival | Espinosa 2025 (null) vs Wang 2019 (unclear) on mortality survival | null vs positive (notable) | | agreement | 1 | Aliberti 2025b | Garcia-Vivanco 2025 | contextual other | Aliberti 2025b (null) vs Garcia-Vivanco 2025 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Aliberti 2025b | Arnold 2010 | contextual other | Aliberti 2025b (null) vs Arnold 2010 (unclear) on contextual other | null vs positive (notable) | | agreement | 1 | Aliberti 2025b | Gavrilov 2011 | contextual other | Aliberti 2025b (null) vs Gavrilov 2011 (null) on contextual other | agreement (minor) | | agreement | 1 | Aliberti 2025b | Balistreri 2012 | contextual other | Aliberti 2025b (null) vs Balistreri 2012 (null) on contextual other | agreement (minor) | | agreement | 1 | Aliberti 2025b | Vitale 2012 | contextual other | Aliberti 2025b (null) vs Vitale 2012 (null) on contextual other | agreement (minor) | | agreement | 1 | Aliberti 2025b | Collino 2013 | contextual other | Aliberti 2025b (null) vs Collino 2013 (null) on contextual other | agreement (minor) | | agreement | 1 | Aliberti 2025b | Garagnani 2013 | contextual other | Aliberti 2025b (null) vs Garagnani 2013 (null) on contextual other | agreement (minor) | | agreement | 1 | Aliberti 2025b | Hazra 2015 | contextual other | Aliberti 2025b (null) vs Hazra 2015 (null) on contextual other | agreement (minor) | | agreement | 1 | Aliberti 2025b | Cai 2016 | contextual other | Aliberti 2025b (null) vs Cai 2016 (null) on contextual other | agreement (minor) | | agreement | 1 | Aliberti 2025b | Santoro 2017 | contextual other | Aliberti 2025b (null) vs Santoro 2017 (null) on contextual other | agreement (minor) | | agreement | 1 | Aliberti 2025b | Wu 2019 | contextual other | Aliberti 2025b (null) vs Wu 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Aliberti 2025b | Gimeno-Miguel 2019 | contextual other | Aliberti 2025b (null) vs Gimeno-Miguel 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Aliberti 2025b | Ruiz 2019 | contextual other | Aliberti 2025b (null) vs Ruiz 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Aliberti 2025b | Beker 2019 | contextual other | Aliberti 2025b (null) vs Beker 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Aliberti 2025b | Santos-Lozano 2020 | contextual other | Aliberti 2025b (null) vs Santos-Lozano 2020 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Aliberti 2025b | Beker 2020 | contextual other | Aliberti 2025b (null) vs Beker 2020 (negative) on contextual other | null vs positive (notable) | | agreement | 1 | Aliberti 2025b | Marston 2021 | contextual other | Aliberti 2025b (null) vs Marston 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Aliberti 2025b | Sebastiani 2021 | contextual other | Aliberti 2025b (null) vs Sebastiani 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Aliberti 2025b | Aiello 2021 | contextual other | Aliberti 2025b (null) vs Aiello 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Aliberti 2025b | Fang 2021 | contextual other | Aliberti 2025b (null) vs Fang 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Aliberti 2025b | Feng 2022 | contextual other | Aliberti 2025b (null) vs Feng 2022 (null) on contextual other | agreement (minor) | | agreement | 1 | Aliberti 2025b | Croize-Pourcelet 2022 | contextual other | Aliberti 2025b (null) vs Croize-Pourcelet 2022 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Aliberti 2025b | Cai 2022 | contextual other | Aliberti 2025b (null) vs Cai 2022 (unclear) on contextual other | null vs positive (notable) | | disagreement | 4 | Aliberti 2025b | Mandala 2023 | contextual other | Aliberti 2025b (null) vs Mandala 2023 (mixed) on contextual other | disagreement (load-bearing) | | agreement | 1 | Aliberti 2025b | Li 2023 | contextual other | Aliberti 2025b (null) vs Li 2023 (null) on contextual other | agreement (minor) | | agreement | 1 | Aliberti 2025c | Aliberti 2025 | longevity | Aliberti 2025c (null) vs Aliberti 2025 (null) on longevity | agreement (minor) | | agreement | 1 | Aliberti 2025c | Govindaraju 2015 | longevity | Aliberti 2025c (null) vs Govindaraju 2015 (null) on longevity | agreement (minor) | | null vs positive | 3 | Aliberti 2025c | Marcon 2020 | longevity | Aliberti 2025c (null) vs Marcon 2020 (positive) on longevity | null vs positive (notable) | | agreement | 1 | Aliberti 2025c | Mazzola 2016 | longevity | Aliberti 2025c (null) vs Mazzola 2016 (null) on longevity | agreement (minor) | | null vs positive | 3 | Garcia-Vivanco 2025 | Arnold 2010 | contextual other | Garcia-Vivanco 2025 (null) vs Arnold 2010 (unclear) on contextual other | null vs positive (notable) | | agreement | 1 | Garcia-Vivanco 2025 | Gavrilov 2011 | contextual other | Garcia-Vivanco 2025 (null) vs Gavrilov 2011 (null) on contextual other | agreement (minor) | | agreement | 1 | Garcia-Vivanco 2025 | Balistreri 2012 | contextual other | Garcia-Vivanco 2025 (null) vs Balistreri 2012 (null) on contextual other | agreement (minor) | | agreement | 1 | Garcia-Vivanco 2025 | Vitale 2012 | contextual other | Garcia-Vivanco 2025 (null) vs Vitale 2012 (null) on contextual other | agreement (minor) | | agreement | 1 | Garcia-Vivanco 2025 | Collino 2013 | contextual other | Garcia-Vivanco 2025 (null) vs Collino 2013 (null) on contextual other | agreement (minor) | | agreement | 1 | Garcia-Vivanco 2025 | Garagnani 2013 | contextual other | Garcia-Vivanco 2025 (null) vs Garagnani 2013 (null) on contextual other | agreement (minor) | | agreement | 1 | Garcia-Vivanco 2025 | Hazra 2015 | contextual other | Garcia-Vivanco 2025 (null) vs Hazra 2015 (null) on contextual other | agreement (minor) | | agreement | 1 | Garcia-Vivanco 2025 | Cai 2016 | contextual other | Garcia-Vivanco 2025 (null) vs Cai 2016 (null) on contextual other | agreement (minor) | | agreement | 1 | Garcia-Vivanco 2025 | Santoro 2017 | contextual other | Garcia-Vivanco 2025 (null) vs Santoro 2017 (null) on contextual other | agreement (minor) | | agreement | 1 | Garcia-Vivanco 2025 | Wu 2019 | contextual other | Garcia-Vivanco 2025 (null) vs Wu 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Garcia-Vivanco 2025 | Gimeno-Miguel 2019 | contextual other | Garcia-Vivanco 2025 (null) vs Gimeno-Miguel 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Garcia-Vivanco 2025 | Ruiz 2019 | contextual other | Garcia-Vivanco 2025 (null) vs Ruiz 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Garcia-Vivanco 2025 | Beker 2019 | contextual other | Garcia-Vivanco 2025 (null) vs Beker 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Garcia-Vivanco 2025 | Santos-Lozano 2020 | contextual other | Garcia-Vivanco 2025 (null) vs Santos-Lozano 2020 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Garcia-Vivanco 2025 | Beker 2020 | contextual other | Garcia-Vivanco 2025 (null) vs Beker 2020 (negative) on contextual other | null vs positive (notable) | | agreement | 1 | Garcia-Vivanco 2025 | Marston 2021 | contextual other | Garcia-Vivanco 2025 (null) vs Marston 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Garcia-Vivanco 2025 | Sebastiani 2021 | contextual other | Garcia-Vivanco 2025 (null) vs Sebastiani 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Garcia-Vivanco 2025 | Aiello 2021 | contextual other | Garcia-Vivanco 2025 (null) vs Aiello 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Garcia-Vivanco 2025 | Fang 2021 | contextual other | Garcia-Vivanco 2025 (null) vs Fang 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Garcia-Vivanco 2025 | Feng 2022 | contextual other | Garcia-Vivanco 2025 (null) vs Feng 2022 (null) on contextual other | agreement (minor) | | agreement | 1 | Garcia-Vivanco 2025 | Croize-Pourcelet 2022 | contextual other | Garcia-Vivanco 2025 (null) vs Croize-Pourcelet 2022 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Garcia-Vivanco 2025 | Cai 2022 | contextual other | Garcia-Vivanco 2025 (null) vs Cai 2022 (unclear) on contextual other | null vs positive (notable) | | disagreement | 4 | Garcia-Vivanco 2025 | Mandala 2023 | contextual other | Garcia-Vivanco 2025 (null) vs Mandala 2023 (mixed) on contextual other | disagreement (load-bearing) | | agreement | 1 | Garcia-Vivanco 2025 | Li 2023 | contextual other | Garcia-Vivanco 2025 (null) vs Li 2023 (null) on contextual other | agreement (minor) | | agreement | 1 | Aliberti 2025 | Govindaraju 2015 | longevity | Aliberti 2025 (null) vs Govindaraju 2015 (null) on longevity | agreement (minor) | | null vs positive | 3 | Aliberti 2025 | Marcon 2020 | longevity | Aliberti 2025 (null) vs Marcon 2020 (positive) on longevity | null vs positive (notable) | | agreement | 1 | Aliberti 2025 | Mazzola 2016 | longevity | Aliberti 2025 (null) vs Mazzola 2016 (null) on longevity | agreement (minor) | | null vs positive | 3 | Suh 2025 | Lindberg 2025 | mortality survival | Suh 2025 (null) vs Lindberg 2025 (unclear) on mortality survival | null vs positive (notable) | | null vs positive | 3 | Suh 2025 | Evans 2014 | mortality survival | Suh 2025 (null) vs Evans 2014 (unclear) on mortality survival | null vs positive (notable) | | null vs positive | 3 | Suh 2025 | Gu 2015 | mortality survival | Suh 2025 (null) vs Gu 2015 (unclear) on mortality survival | null vs positive (notable) | | null vs positive | 3 | Suh 2025 | Wang 2019 | mortality survival | Suh 2025 (null) vs Wang 2019 (unclear) on mortality survival | null vs positive (notable) | | agreement | 1 | Lindberg 2025 | Evans 2014 | mortality survival | Lindberg 2025 (unclear) vs Evans 2014 (unclear) on mortality survival | agreement (minor) | | agreement | 1 | Lindberg 2025 | Gu 2015 | mortality survival | Lindberg 2025 (unclear) vs Gu 2015 (unclear) on mortality survival | agreement (minor) | | agreement | 1 | Lindberg 2025 | Wang 2019 | mortality survival | Lindberg 2025 (unclear) vs Wang 2019 (unclear) on mortality survival | agreement (minor) | | null vs positive | 3 | Arnold 2010 | Gavrilov 2011 | contextual other | Arnold 2010 (unclear) vs Gavrilov 2011 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Arnold 2010 | Balistreri 2012 | contextual other | Arnold 2010 (unclear) vs Balistreri 2012 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Arnold 2010 | Vitale 2012 | contextual other | Arnold 2010 (unclear) vs Vitale 2012 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Arnold 2010 | Collino 2013 | contextual other | Arnold 2010 (unclear) vs Collino 2013 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Arnold 2010 | Garagnani 2013 | contextual other | Arnold 2010 (unclear) vs Garagnani 2013 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Arnold 2010 | Hazra 2015 | contextual other | Arnold 2010 (unclear) vs Hazra 2015 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Arnold 2010 | Cai 2016 | contextual other | Arnold 2010 (unclear) vs Cai 2016 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Arnold 2010 | Santoro 2017 | contextual other | Arnold 2010 (unclear) vs Santoro 2017 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Arnold 2010 | Wu 2019 | contextual other | Arnold 2010 (unclear) vs Wu 2019 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Arnold 2010 | Gimeno-Miguel 2019 | contextual other | Arnold 2010 (unclear) vs Gimeno-Miguel 2019 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Arnold 2010 | Ruiz 2019 | contextual other | Arnold 2010 (unclear) vs Ruiz 2019 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Arnold 2010 | Beker 2019 | contextual other | Arnold 2010 (unclear) vs Beker 2019 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Arnold 2010 | Santos-Lozano 2020 | contextual other | Arnold 2010 (unclear) vs Santos-Lozano 2020 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Arnold 2010 | Marston 2021 | contextual other | Arnold 2010 (unclear) vs Marston 2021 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Arnold 2010 | Sebastiani 2021 | contextual other | Arnold 2010 (unclear) vs Sebastiani 2021 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Arnold 2010 | Aiello 2021 | contextual other | Arnold 2010 (unclear) vs Aiello 2021 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Arnold 2010 | Fang 2021 | contextual other | Arnold 2010 (unclear) vs Fang 2021 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Arnold 2010 | Feng 2022 | contextual other | Arnold 2010 (unclear) vs Feng 2022 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Arnold 2010 | Croize-Pourcelet 2022 | contextual other | Arnold 2010 (unclear) vs Croize-Pourcelet 2022 (null) on contextual other | null vs positive (notable) | | agreement | 1 | Arnold 2010 | Cai 2022 | contextual other | Arnold 2010 (unclear) vs Cai 2022 (unclear) on contextual other | agreement (minor) | | disagreement | 4 | Arnold 2010 | Mandala 2023 | contextual other | Arnold 2010 (unclear) vs Mandala 2023 (mixed) on contextual other | disagreement (load-bearing) | | null vs positive | 3 | Arnold 2010 | Li 2023 | contextual other | Arnold 2010 (unclear) vs Li 2023 (null) on contextual other | null vs positive (notable) | | agreement | 1 | Gavrilov 2011 | Balistreri 2012 | contextual other | Gavrilov 2011 (null) vs Balistreri 2012 (null) on contextual other | agreement (minor) | | agreement | 1 | Gavrilov 2011 | Vitale 2012 | contextual other | Gavrilov 2011 (null) vs Vitale 2012 (null) on contextual other | agreement (minor) | | agreement | 1 | Gavrilov 2011 | Collino 2013 | contextual other | Gavrilov 2011 (null) vs Collino 2013 (null) on contextual other | agreement (minor) | | agreement | 1 | Gavrilov 2011 | Garagnani 2013 | contextual other | Gavrilov 2011 (null) vs Garagnani 2013 (null) on contextual other | agreement (minor) | | agreement | 1 | Gavrilov 2011 | Hazra 2015 | contextual other | Gavrilov 2011 (null) vs Hazra 2015 (null) on contextual other | agreement (minor) | | agreement | 1 | Gavrilov 2011 | Cai 2016 | contextual other | Gavrilov 2011 (null) vs Cai 2016 (null) on contextual other | agreement (minor) | | agreement | 1 | Gavrilov 2011 | Santoro 2017 | contextual other | Gavrilov 2011 (null) vs Santoro 2017 (null) on contextual other | agreement (minor) | | agreement | 1 | Gavrilov 2011 | Wu 2019 | contextual other | Gavrilov 2011 (null) vs Wu 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Gavrilov 2011 | Gimeno-Miguel 2019 | contextual other | Gavrilov 2011 (null) vs Gimeno-Miguel 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Gavrilov 2011 | Ruiz 2019 | contextual other | Gavrilov 2011 (null) vs Ruiz 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Gavrilov 2011 | Beker 2019 | contextual other | Gavrilov 2011 (null) vs Beker 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Gavrilov 2011 | Santos-Lozano 2020 | contextual other | Gavrilov 2011 (null) vs Santos-Lozano 2020 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Gavrilov 2011 | Beker 2020 | contextual other | Gavrilov 2011 (null) vs Beker 2020 (negative) on contextual other | null vs positive (notable) | | agreement | 1 | Gavrilov 2011 | Marston 2021 | contextual other | Gavrilov 2011 (null) vs Marston 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Gavrilov 2011 | Sebastiani 2021 | contextual other | Gavrilov 2011 (null) vs Sebastiani 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Gavrilov 2011 | Aiello 2021 | contextual other | Gavrilov 2011 (null) vs Aiello 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Gavrilov 2011 | Fang 2021 | contextual other | Gavrilov 2011 (null) vs Fang 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Gavrilov 2011 | Feng 2022 | contextual other | Gavrilov 2011 (null) vs Feng 2022 (null) on contextual other | agreement (minor) | | agreement | 1 | Gavrilov 2011 | Croize-Pourcelet 2022 | contextual other | Gavrilov 2011 (null) vs Croize-Pourcelet 2022 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Gavrilov 2011 | Cai 2022 | contextual other | Gavrilov 2011 (null) vs Cai 2022 (unclear) on contextual other | null vs positive (notable) | | disagreement | 4 | Gavrilov 2011 | Mandala 2023 | contextual other | Gavrilov 2011 (null) vs Mandala 2023 (mixed) on contextual other | disagreement (load-bearing) | | agreement | 1 | Gavrilov 2011 | Li 2023 | contextual other | Gavrilov 2011 (null) vs Li 2023 (null) on contextual other | agreement (minor) | | agreement | 1 | Balistreri 2012 | Vitale 2012 | contextual other | Balistreri 2012 (null) vs Vitale 2012 (null) on contextual other | agreement (minor) | | agreement | 1 | Balistreri 2012 | Collino 2013 | contextual other | Balistreri 2012 (null) vs Collino 2013 (null) on contextual other | agreement (minor) | | agreement | 1 | Balistreri 2012 | Garagnani 2013 | contextual other | Balistreri 2012 (null) vs Garagnani 2013 (null) on contextual other | agreement (minor) | | agreement | 1 | Balistreri 2012 | Hazra 2015 | contextual other | Balistreri 2012 (null) vs Hazra 2015 (null) on contextual other | agreement (minor) | | agreement | 1 | Balistreri 2012 | Cai 2016 | contextual other | Balistreri 2012 (null) vs Cai 2016 (null) on contextual other | agreement (minor) | | agreement | 1 | Balistreri 2012 | Santoro 2017 | contextual other | Balistreri 2012 (null) vs Santoro 2017 (null) on contextual other | agreement (minor) | | agreement | 1 | Balistreri 2012 | Wu 2019 | contextual other | Balistreri 2012 (null) vs Wu 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Balistreri 2012 | Gimeno-Miguel 2019 | contextual other | Balistreri 2012 (null) vs Gimeno-Miguel 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Balistreri 2012 | Ruiz 2019 | contextual other | Balistreri 2012 (null) vs Ruiz 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Balistreri 2012 | Beker 2019 | contextual other | Balistreri 2012 (null) vs Beker 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Balistreri 2012 | Santos-Lozano 2020 | contextual other | Balistreri 2012 (null) vs Santos-Lozano 2020 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Balistreri 2012 | Beker 2020 | contextual other | Balistreri 2012 (null) vs Beker 2020 (negative) on contextual other | null vs positive (notable) | | agreement | 1 | Balistreri 2012 | Marston 2021 | contextual other | Balistreri 2012 (null) vs Marston 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Balistreri 2012 | Sebastiani 2021 | contextual other | Balistreri 2012 (null) vs Sebastiani 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Balistreri 2012 | Aiello 2021 | contextual other | Balistreri 2012 (null) vs Aiello 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Balistreri 2012 | Fang 2021 | contextual other | Balistreri 2012 (null) vs Fang 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Balistreri 2012 | Feng 2022 | contextual other | Balistreri 2012 (null) vs Feng 2022 (null) on contextual other | agreement (minor) | | agreement | 1 | Balistreri 2012 | Croize-Pourcelet 2022 | contextual other | Balistreri 2012 (null) vs Croize-Pourcelet 2022 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Balistreri 2012 | Cai 2022 | contextual other | Balistreri 2012 (null) vs Cai 2022 (unclear) on contextual other | null vs positive (notable) | | disagreement | 4 | Balistreri 2012 | Mandala 2023 | contextual other | Balistreri 2012 (null) vs Mandala 2023 (mixed) on contextual other | disagreement (load-bearing) | | agreement | 1 | Balistreri 2012 | Li 2023 | contextual other | Balistreri 2012 (null) vs Li 2023 (null) on contextual other | agreement (minor) | | agreement | 1 | Vitale 2012 | Collino 2013 | contextual other | Vitale 2012 (null) vs Collino 2013 (null) on contextual other | agreement (minor) | | agreement | 1 | Vitale 2012 | Garagnani 2013 | contextual other | Vitale 2012 (null) vs Garagnani 2013 (null) on contextual other | agreement (minor) | | agreement | 1 | Vitale 2012 | Hazra 2015 | contextual other | Vitale 2012 (null) vs Hazra 2015 (null) on contextual other | agreement (minor) | | agreement | 1 | Vitale 2012 | Cai 2016 | contextual other | Vitale 2012 (null) vs Cai 2016 (null) on contextual other | agreement (minor) | | agreement | 1 | Vitale 2012 | Santoro 2017 | contextual other | Vitale 2012 (null) vs Santoro 2017 (null) on contextual other | agreement (minor) | | agreement | 1 | Vitale 2012 | Wu 2019 | contextual other | Vitale 2012 (null) vs Wu 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Vitale 2012 | Gimeno-Miguel 2019 | contextual other | Vitale 2012 (null) vs Gimeno-Miguel 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Vitale 2012 | Ruiz 2019 | contextual other | Vitale 2012 (null) vs Ruiz 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Vitale 2012 | Beker 2019 | contextual other | Vitale 2012 (null) vs Beker 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Vitale 2012 | Santos-Lozano 2020 | contextual other | Vitale 2012 (null) vs Santos-Lozano 2020 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Vitale 2012 | Beker 2020 | contextual other | Vitale 2012 (null) vs Beker 2020 (negative) on contextual other | null vs positive (notable) | | agreement | 1 | Vitale 2012 | Marston 2021 | contextual other | Vitale 2012 (null) vs Marston 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Vitale 2012 | Sebastiani 2021 | contextual other | Vitale 2012 (null) vs Sebastiani 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Vitale 2012 | Aiello 2021 | contextual other | Vitale 2012 (null) vs Aiello 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Vitale 2012 | Fang 2021 | contextual other | Vitale 2012 (null) vs Fang 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Vitale 2012 | Feng 2022 | contextual other | Vitale 2012 (null) vs Feng 2022 (null) on contextual other | agreement (minor) | | agreement | 1 | Vitale 2012 | Croize-Pourcelet 2022 | contextual other | Vitale 2012 (null) vs Croize-Pourcelet 2022 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Vitale 2012 | Cai 2022 | contextual other | Vitale 2012 (null) vs Cai 2022 (unclear) on contextual other | null vs positive (notable) | | disagreement | 4 | Vitale 2012 | Mandala 2023 | contextual other | Vitale 2012 (null) vs Mandala 2023 (mixed) on contextual other | disagreement (load-bearing) | | agreement | 1 | Vitale 2012 | Li 2023 | contextual other | Vitale 2012 (null) vs Li 2023 (null) on contextual other | agreement (minor) | | agreement | 1 | Collino 2013 | Garagnani 2013 | contextual other | Collino 2013 (null) vs Garagnani 2013 (null) on contextual other | agreement (minor) | | agreement | 1 | Collino 2013 | Hazra 2015 | contextual other | Collino 2013 (null) vs Hazra 2015 (null) on contextual other | agreement (minor) | | agreement | 1 | Collino 2013 | Cai 2016 | contextual other | Collino 2013 (null) vs Cai 2016 (null) on contextual other | agreement (minor) | | agreement | 1 | Collino 2013 | Santoro 2017 | contextual other | Collino 2013 (null) vs Santoro 2017 (null) on contextual other | agreement (minor) | | agreement | 1 | Collino 2013 | Wu 2019 | contextual other | Collino 2013 (null) vs Wu 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Collino 2013 | Gimeno-Miguel 2019 | contextual other | Collino 2013 (null) vs Gimeno-Miguel 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Collino 2013 | Ruiz 2019 | contextual other | Collino 2013 (null) vs Ruiz 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Collino 2013 | Beker 2019 | contextual other | Collino 2013 (null) vs Beker 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Collino 2013 | Santos-Lozano 2020 | contextual other | Collino 2013 (null) vs Santos-Lozano 2020 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Collino 2013 | Beker 2020 | contextual other | Collino 2013 (null) vs Beker 2020 (negative) on contextual other | null vs positive (notable) | | agreement | 1 | Collino 2013 | Marston 2021 | contextual other | Collino 2013 (null) vs Marston 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Collino 2013 | Sebastiani 2021 | contextual other | Collino 2013 (null) vs Sebastiani 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Collino 2013 | Aiello 2021 | contextual other | Collino 2013 (null) vs Aiello 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Collino 2013 | Fang 2021 | contextual other | Collino 2013 (null) vs Fang 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Collino 2013 | Feng 2022 | contextual other | Collino 2013 (null) vs Feng 2022 (null) on contextual other | agreement (minor) | | agreement | 1 | Collino 2013 | Croize-Pourcelet 2022 | contextual other | Collino 2013 (null) vs Croize-Pourcelet 2022 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Collino 2013 | Cai 2022 | contextual other | Collino 2013 (null) vs Cai 2022 (unclear) on contextual other | null vs positive (notable) | | disagreement | 4 | Collino 2013 | Mandala 2023 | contextual other | Collino 2013 (null) vs Mandala 2023 (mixed) on contextual other | disagreement (load-bearing) | | agreement | 1 | Collino 2013 | Li 2023 | contextual other | Collino 2013 (null) vs Li 2023 (null) on contextual other | agreement (minor) | | agreement | 1 | Garagnani 2013 | Hazra 2015 | contextual other | Garagnani 2013 (null) vs Hazra 2015 (null) on contextual other | agreement (minor) | | agreement | 1 | Garagnani 2013 | Cai 2016 | contextual other | Garagnani 2013 (null) vs Cai 2016 (null) on contextual other | agreement (minor) | | agreement | 1 | Garagnani 2013 | Santoro 2017 | contextual other | Garagnani 2013 (null) vs Santoro 2017 (null) on contextual other | agreement (minor) | | agreement | 1 | Garagnani 2013 | Wu 2019 | contextual other | Garagnani 2013 (null) vs Wu 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Garagnani 2013 | Gimeno-Miguel 2019 | contextual other | Garagnani 2013 (null) vs Gimeno-Miguel 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Garagnani 2013 | Ruiz 2019 | contextual other | Garagnani 2013 (null) vs Ruiz 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Garagnani 2013 | Beker 2019 | contextual other | Garagnani 2013 (null) vs Beker 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Garagnani 2013 | Santos-Lozano 2020 | contextual other | Garagnani 2013 (null) vs Santos-Lozano 2020 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Garagnani 2013 | Beker 2020 | contextual other | Garagnani 2013 (null) vs Beker 2020 (negative) on contextual other | null vs positive (notable) | | agreement | 1 | Garagnani 2013 | Marston 2021 | contextual other | Garagnani 2013 (null) vs Marston 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Garagnani 2013 | Sebastiani 2021 | contextual other | Garagnani 2013 (null) vs Sebastiani 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Garagnani 2013 | Aiello 2021 | contextual other | Garagnani 2013 (null) vs Aiello 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Garagnani 2013 | Fang 2021 | contextual other | Garagnani 2013 (null) vs Fang 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Garagnani 2013 | Feng 2022 | contextual other | Garagnani 2013 (null) vs Feng 2022 (null) on contextual other | agreement (minor) | | agreement | 1 | Garagnani 2013 | Croize-Pourcelet 2022 | contextual other | Garagnani 2013 (null) vs Croize-Pourcelet 2022 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Garagnani 2013 | Cai 2022 | contextual other | Garagnani 2013 (null) vs Cai 2022 (unclear) on contextual other | null vs positive (notable) | | disagreement | 4 | Garagnani 2013 | Mandala 2023 | contextual other | Garagnani 2013 (null) vs Mandala 2023 (mixed) on contextual other | disagreement (load-bearing) | | agreement | 1 | Garagnani 2013 | Li 2023 | contextual other | Garagnani 2013 (null) vs Li 2023 (null) on contextual other | agreement (minor) | | agreement | 1 | Evans 2014 | Gu 2015 | mortality survival | Evans 2014 (unclear) vs Gu 2015 (unclear) on mortality survival | agreement (minor) | | agreement | 1 | Evans 2014 | Wang 2019 | mortality survival | Evans 2014 (unclear) vs Wang 2019 (unclear) on mortality survival | agreement (minor) | | agreement | 1 | Gu 2015 | Wang 2019 | mortality survival | Gu 2015 (unclear) vs Wang 2019 (unclear) on mortality survival | agreement (minor) | | agreement | 1 | Hazra 2015 | Cai 2016 | contextual other | Hazra 2015 (null) vs Cai 2016 (null) on contextual other | agreement (minor) | | agreement | 1 | Hazra 2015 | Santoro 2017 | contextual other | Hazra 2015 (null) vs Santoro 2017 (null) on contextual other | agreement (minor) | | agreement | 1 | Hazra 2015 | Wu 2019 | contextual other | Hazra 2015 (null) vs Wu 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Hazra 2015 | Gimeno-Miguel 2019 | contextual other | Hazra 2015 (null) vs Gimeno-Miguel 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Hazra 2015 | Ruiz 2019 | contextual other | Hazra 2015 (null) vs Ruiz 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Hazra 2015 | Beker 2019 | contextual other | Hazra 2015 (null) vs Beker 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Hazra 2015 | Santos-Lozano 2020 | contextual other | Hazra 2015 (null) vs Santos-Lozano 2020 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Hazra 2015 | Beker 2020 | contextual other | Hazra 2015 (null) vs Beker 2020 (negative) on contextual other | null vs positive (notable) | | agreement | 1 | Hazra 2015 | Marston 2021 | contextual other | Hazra 2015 (null) vs Marston 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Hazra 2015 | Sebastiani 2021 | contextual other | Hazra 2015 (null) vs Sebastiani 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Hazra 2015 | Aiello 2021 | contextual other | Hazra 2015 (null) vs Aiello 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Hazra 2015 | Fang 2021 | contextual other | Hazra 2015 (null) vs Fang 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Hazra 2015 | Feng 2022 | contextual other | Hazra 2015 (null) vs Feng 2022 (null) on contextual other | agreement (minor) | | agreement | 1 | Hazra 2015 | Croize-Pourcelet 2022 | contextual other | Hazra 2015 (null) vs Croize-Pourcelet 2022 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Hazra 2015 | Cai 2022 | contextual other | Hazra 2015 (null) vs Cai 2022 (unclear) on contextual other | null vs positive (notable) | | disagreement | 4 | Hazra 2015 | Mandala 2023 | contextual other | Hazra 2015 (null) vs Mandala 2023 (mixed) on contextual other | disagreement (load-bearing) | | agreement | 1 | Hazra 2015 | Li 2023 | contextual other | Hazra 2015 (null) vs Li 2023 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Govindaraju 2015 | Marcon 2020 | longevity | Govindaraju 2015 (null) vs Marcon 2020 (positive) on longevity | null vs positive (notable) | | agreement | 1 | Govindaraju 2015 | Mazzola 2016 | longevity | Govindaraju 2015 (null) vs Mazzola 2016 (null) on longevity | agreement (minor) | | agreement | 1 | Cai 2016 | Santoro 2017 | contextual other | Cai 2016 (null) vs Santoro 2017 (null) on contextual other | agreement (minor) | | agreement | 1 | Cai 2016 | Wu 2019 | contextual other | Cai 2016 (null) vs Wu 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Cai 2016 | Gimeno-Miguel 2019 | contextual other | Cai 2016 (null) vs Gimeno-Miguel 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Cai 2016 | Ruiz 2019 | contextual other | Cai 2016 (null) vs Ruiz 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Cai 2016 | Beker 2019 | contextual other | Cai 2016 (null) vs Beker 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Cai 2016 | Santos-Lozano 2020 | contextual other | Cai 2016 (null) vs Santos-Lozano 2020 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Cai 2016 | Beker 2020 | contextual other | Cai 2016 (null) vs Beker 2020 (negative) on contextual other | null vs positive (notable) | | agreement | 1 | Cai 2016 | Marston 2021 | contextual other | Cai 2016 (null) vs Marston 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Cai 2016 | Sebastiani 2021 | contextual other | Cai 2016 (null) vs Sebastiani 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Cai 2016 | Aiello 2021 | contextual other | Cai 2016 (null) vs Aiello 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Cai 2016 | Fang 2021 | contextual other | Cai 2016 (null) vs Fang 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Cai 2016 | Feng 2022 | contextual other | Cai 2016 (null) vs Feng 2022 (null) on contextual other | agreement (minor) | | agreement | 1 | Cai 2016 | Croize-Pourcelet 2022 | contextual other | Cai 2016 (null) vs Croize-Pourcelet 2022 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Cai 2016 | Cai 2022 | contextual other | Cai 2016 (null) vs Cai 2022 (unclear) on contextual other | null vs positive (notable) | | disagreement | 4 | Cai 2016 | Mandala 2023 | contextual other | Cai 2016 (null) vs Mandala 2023 (mixed) on contextual other | disagreement (load-bearing) | | agreement | 1 | Cai 2016 | Li 2023 | contextual other | Cai 2016 (null) vs Li 2023 (null) on contextual other | agreement (minor) | | agreement | 1 | Santoro 2017 | Wu 2019 | contextual other | Santoro 2017 (null) vs Wu 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Santoro 2017 | Gimeno-Miguel 2019 | contextual other | Santoro 2017 (null) vs Gimeno-Miguel 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Santoro 2017 | Ruiz 2019 | contextual other | Santoro 2017 (null) vs Ruiz 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Santoro 2017 | Beker 2019 | contextual other | Santoro 2017 (null) vs Beker 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Santoro 2017 | Santos-Lozano 2020 | contextual other | Santoro 2017 (null) vs Santos-Lozano 2020 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Santoro 2017 | Beker 2020 | contextual other | Santoro 2017 (null) vs Beker 2020 (negative) on contextual other | null vs positive (notable) | | agreement | 1 | Santoro 2017 | Marston 2021 | contextual other | Santoro 2017 (null) vs Marston 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Santoro 2017 | Sebastiani 2021 | contextual other | Santoro 2017 (null) vs Sebastiani 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Santoro 2017 | Aiello 2021 | contextual other | Santoro 2017 (null) vs Aiello 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Santoro 2017 | Fang 2021 | contextual other | Santoro 2017 (null) vs Fang 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Santoro 2017 | Feng 2022 | contextual other | Santoro 2017 (null) vs Feng 2022 (null) on contextual other | agreement (minor) | | agreement | 1 | Santoro 2017 | Croize-Pourcelet 2022 | contextual other | Santoro 2017 (null) vs Croize-Pourcelet 2022 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Santoro 2017 | Cai 2022 | contextual other | Santoro 2017 (null) vs Cai 2022 (unclear) on contextual other | null vs positive (notable) | | disagreement | 4 | Santoro 2017 | Mandala 2023 | contextual other | Santoro 2017 (null) vs Mandala 2023 (mixed) on contextual other | disagreement (load-bearing) | | agreement | 1 | Santoro 2017 | Li 2023 | contextual other | Santoro 2017 (null) vs Li 2023 (null) on contextual other | agreement (minor) | | agreement | 1 | Wu 2019 | Gimeno-Miguel 2019 | contextual other | Wu 2019 (null) vs Gimeno-Miguel 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Wu 2019 | Ruiz 2019 | contextual other | Wu 2019 (null) vs Ruiz 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Wu 2019 | Beker 2019 | contextual other | Wu 2019 (null) vs Beker 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Wu 2019 | Santos-Lozano 2020 | contextual other | Wu 2019 (null) vs Santos-Lozano 2020 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Wu 2019 | Beker 2020 | contextual other | Wu 2019 (null) vs Beker 2020 (negative) on contextual other | null vs positive (notable) | | agreement | 1 | Wu 2019 | Marston 2021 | contextual other | Wu 2019 (null) vs Marston 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Wu 2019 | Sebastiani 2021 | contextual other | Wu 2019 (null) vs Sebastiani 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Wu 2019 | Aiello 2021 | contextual other | Wu 2019 (null) vs Aiello 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Wu 2019 | Fang 2021 | contextual other | Wu 2019 (null) vs Fang 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Wu 2019 | Feng 2022 | contextual other | Wu 2019 (null) vs Feng 2022 (null) on contextual other | agreement (minor) | | agreement | 1 | Wu 2019 | Croize-Pourcelet 2022 | contextual other | Wu 2019 (null) vs Croize-Pourcelet 2022 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Wu 2019 | Cai 2022 | contextual other | Wu 2019 (null) vs Cai 2022 (unclear) on contextual other | null vs positive (notable) | | disagreement | 4 | Wu 2019 | Mandala 2023 | contextual other | Wu 2019 (null) vs Mandala 2023 (mixed) on contextual other | disagreement (load-bearing) | | agreement | 1 | Wu 2019 | Li 2023 | contextual other | Wu 2019 (null) vs Li 2023 (null) on contextual other | agreement (minor) | | agreement | 1 | Gimeno-Miguel 2019 | Ruiz 2019 | contextual other | Gimeno-Miguel 2019 (null) vs Ruiz 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Gimeno-Miguel 2019 | Beker 2019 | contextual other | Gimeno-Miguel 2019 (null) vs Beker 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Gimeno-Miguel 2019 | Santos-Lozano 2020 | contextual other | Gimeno-Miguel 2019 (null) vs Santos-Lozano 2020 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Gimeno-Miguel 2019 | Beker 2020 | contextual other | Gimeno-Miguel 2019 (null) vs Beker 2020 (negative) on contextual other | null vs positive (notable) | | agreement | 1 | Gimeno-Miguel 2019 | Marston 2021 | contextual other | Gimeno-Miguel 2019 (null) vs Marston 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Gimeno-Miguel 2019 | Sebastiani 2021 | contextual other | Gimeno-Miguel 2019 (null) vs Sebastiani 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Gimeno-Miguel 2019 | Aiello 2021 | contextual other | Gimeno-Miguel 2019 (null) vs Aiello 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Gimeno-Miguel 2019 | Fang 2021 | contextual other | Gimeno-Miguel 2019 (null) vs Fang 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Gimeno-Miguel 2019 | Feng 2022 | contextual other | Gimeno-Miguel 2019 (null) vs Feng 2022 (null) on contextual other | agreement (minor) | | agreement | 1 | Gimeno-Miguel 2019 | Croize-Pourcelet 2022 | contextual other | Gimeno-Miguel 2019 (null) vs Croize-Pourcelet 2022 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Gimeno-Miguel 2019 | Cai 2022 | contextual other | Gimeno-Miguel 2019 (null) vs Cai 2022 (unclear) on contextual other | null vs positive (notable) | | disagreement | 4 | Gimeno-Miguel 2019 | Mandala 2023 | contextual other | Gimeno-Miguel 2019 (null) vs Mandala 2023 (mixed) on contextual other | disagreement (load-bearing) | | agreement | 1 | Gimeno-Miguel 2019 | Li 2023 | contextual other | Gimeno-Miguel 2019 (null) vs Li 2023 (null) on contextual other | agreement (minor) | | agreement | 1 | Ruiz 2019 | Beker 2019 | contextual other | Ruiz 2019 (null) vs Beker 2019 (null) on contextual other | agreement (minor) | | agreement | 1 | Ruiz 2019 | Santos-Lozano 2020 | contextual other | Ruiz 2019 (null) vs Santos-Lozano 2020 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Ruiz 2019 | Beker 2020 | contextual other | Ruiz 2019 (null) vs Beker 2020 (negative) on contextual other | null vs positive (notable) | | agreement | 1 | Ruiz 2019 | Marston 2021 | contextual other | Ruiz 2019 (null) vs Marston 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Ruiz 2019 | Sebastiani 2021 | contextual other | Ruiz 2019 (null) vs Sebastiani 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Ruiz 2019 | Aiello 2021 | contextual other | Ruiz 2019 (null) vs Aiello 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Ruiz 2019 | Fang 2021 | contextual other | Ruiz 2019 (null) vs Fang 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Ruiz 2019 | Feng 2022 | contextual other | Ruiz 2019 (null) vs Feng 2022 (null) on contextual other | agreement (minor) | | agreement | 1 | Ruiz 2019 | Croize-Pourcelet 2022 | contextual other | Ruiz 2019 (null) vs Croize-Pourcelet 2022 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Ruiz 2019 | Cai 2022 | contextual other | Ruiz 2019 (null) vs Cai 2022 (unclear) on contextual other | null vs positive (notable) | | disagreement | 4 | Ruiz 2019 | Mandala 2023 | contextual other | Ruiz 2019 (null) vs Mandala 2023 (mixed) on contextual other | disagreement (load-bearing) | | agreement | 1 | Ruiz 2019 | Li 2023 | contextual other | Ruiz 2019 (null) vs Li 2023 (null) on contextual other | agreement (minor) | | agreement | 1 | Beker 2019 | Santos-Lozano 2020 | contextual other | Beker 2019 (null) vs Santos-Lozano 2020 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Beker 2019 | Beker 2020 | contextual other | Beker 2019 (null) vs Beker 2020 (negative) on contextual other | null vs positive (notable) | | agreement | 1 | Beker 2019 | Marston 2021 | contextual other | Beker 2019 (null) vs Marston 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Beker 2019 | Sebastiani 2021 | contextual other | Beker 2019 (null) vs Sebastiani 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Beker 2019 | Aiello 2021 | contextual other | Beker 2019 (null) vs Aiello 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Beker 2019 | Fang 2021 | contextual other | Beker 2019 (null) vs Fang 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Beker 2019 | Feng 2022 | contextual other | Beker 2019 (null) vs Feng 2022 (null) on contextual other | agreement (minor) | | agreement | 1 | Beker 2019 | Croize-Pourcelet 2022 | contextual other | Beker 2019 (null) vs Croize-Pourcelet 2022 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Beker 2019 | Cai 2022 | contextual other | Beker 2019 (null) vs Cai 2022 (unclear) on contextual other | null vs positive (notable) | | disagreement | 4 | Beker 2019 | Mandala 2023 | contextual other | Beker 2019 (null) vs Mandala 2023 (mixed) on contextual other | disagreement (load-bearing) | | agreement | 1 | Beker 2019 | Li 2023 | contextual other | Beker 2019 (null) vs Li 2023 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Santos-Lozano 2020 | Beker 2020 | contextual other | Santos-Lozano 2020 (null) vs Beker 2020 (negative) on contextual other | null vs positive (notable) | | agreement | 1 | Santos-Lozano 2020 | Marston 2021 | contextual other | Santos-Lozano 2020 (null) vs Marston 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Santos-Lozano 2020 | Sebastiani 2021 | contextual other | Santos-Lozano 2020 (null) vs Sebastiani 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Santos-Lozano 2020 | Aiello 2021 | contextual other | Santos-Lozano 2020 (null) vs Aiello 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Santos-Lozano 2020 | Fang 2021 | contextual other | Santos-Lozano 2020 (null) vs Fang 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Santos-Lozano 2020 | Feng 2022 | contextual other | Santos-Lozano 2020 (null) vs Feng 2022 (null) on contextual other | agreement (minor) | | agreement | 1 | Santos-Lozano 2020 | Croize-Pourcelet 2022 | contextual other | Santos-Lozano 2020 (null) vs Croize-Pourcelet 2022 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Santos-Lozano 2020 | Cai 2022 | contextual other | Santos-Lozano 2020 (null) vs Cai 2022 (unclear) on contextual other | null vs positive (notable) | | disagreement | 4 | Santos-Lozano 2020 | Mandala 2023 | contextual other | Santos-Lozano 2020 (null) vs Mandala 2023 (mixed) on contextual other | disagreement (load-bearing) | | agreement | 1 | Santos-Lozano 2020 | Li 2023 | contextual other | Santos-Lozano 2020 (null) vs Li 2023 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Beker 2020 | Marston 2021 | contextual other | Beker 2020 (negative) vs Marston 2021 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Beker 2020 | Sebastiani 2021 | contextual other | Beker 2020 (negative) vs Sebastiani 2021 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Beker 2020 | Aiello 2021 | contextual other | Beker 2020 (negative) vs Aiello 2021 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Beker 2020 | Fang 2021 | contextual other | Beker 2020 (negative) vs Fang 2021 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Beker 2020 | Feng 2022 | contextual other | Beker 2020 (negative) vs Feng 2022 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Beker 2020 | Croize-Pourcelet 2022 | contextual other | Beker 2020 (negative) vs Croize-Pourcelet 2022 (null) on contextual other | null vs positive (notable) | | disagreement | 4 | Beker 2020 | Mandala 2023 | contextual other | Beker 2020 (negative) vs Mandala 2023 (mixed) on contextual other | disagreement (load-bearing) | | null vs positive | 3 | Beker 2020 | Li 2023 | contextual other | Beker 2020 (negative) vs Li 2023 (null) on contextual other | null vs positive (notable) | | null vs positive | 3 | Marcon 2020 | Mazzola 2016 | longevity | Marcon 2020 (positive) vs Mazzola 2016 (null) on longevity | null vs positive (notable) | | agreement | 1 | Marston 2021 | Sebastiani 2021 | contextual other | Marston 2021 (null) vs Sebastiani 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Marston 2021 | Aiello 2021 | contextual other | Marston 2021 (null) vs Aiello 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Marston 2021 | Fang 2021 | contextual other | Marston 2021 (null) vs Fang 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Marston 2021 | Feng 2022 | contextual other | Marston 2021 (null) vs Feng 2022 (null) on contextual other | agreement (minor) | | agreement | 1 | Marston 2021 | Croize-Pourcelet 2022 | contextual other | Marston 2021 (null) vs Croize-Pourcelet 2022 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Marston 2021 | Cai 2022 | contextual other | Marston 2021 (null) vs Cai 2022 (unclear) on contextual other | null vs positive (notable) | | disagreement | 4 | Marston 2021 | Mandala 2023 | contextual other | Marston 2021 (null) vs Mandala 2023 (mixed) on contextual other | disagreement (load-bearing) | | agreement | 1 | Marston 2021 | Li 2023 | contextual other | Marston 2021 (null) vs Li 2023 (null) on contextual other | agreement (minor) | | agreement | 1 | Sebastiani 2021 | Aiello 2021 | contextual other | Sebastiani 2021 (null) vs Aiello 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Sebastiani 2021 | Fang 2021 | contextual other | Sebastiani 2021 (null) vs Fang 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Sebastiani 2021 | Feng 2022 | contextual other | Sebastiani 2021 (null) vs Feng 2022 (null) on contextual other | agreement (minor) | | agreement | 1 | Sebastiani 2021 | Croize-Pourcelet 2022 | contextual other | Sebastiani 2021 (null) vs Croize-Pourcelet 2022 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Sebastiani 2021 | Cai 2022 | contextual other | Sebastiani 2021 (null) vs Cai 2022 (unclear) on contextual other | null vs positive (notable) | | disagreement | 4 | Sebastiani 2021 | Mandala 2023 | contextual other | Sebastiani 2021 (null) vs Mandala 2023 (mixed) on contextual other | disagreement (load-bearing) | | agreement | 1 | Sebastiani 2021 | Li 2023 | contextual other | Sebastiani 2021 (null) vs Li 2023 (null) on contextual other | agreement (minor) | | agreement | 1 | Aiello 2021 | Fang 2021 | contextual other | Aiello 2021 (null) vs Fang 2021 (null) on contextual other | agreement (minor) | | agreement | 1 | Aiello 2021 | Feng 2022 | contextual other | Aiello 2021 (null) vs Feng 2022 (null) on contextual other | agreement (minor) | | agreement | 1 | Aiello 2021 | Croize-Pourcelet 2022 | contextual other | Aiello 2021 (null) vs Croize-Pourcelet 2022 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Aiello 2021 | Cai 2022 | contextual other | Aiello 2021 (null) vs Cai 2022 (unclear) on contextual other | null vs positive (notable) | | disagreement | 4 | Aiello 2021 | Mandala 2023 | contextual other | Aiello 2021 (null) vs Mandala 2023 (mixed) on contextual other | disagreement (load-bearing) | | agreement | 1 | Aiello 2021 | Li 2023 | contextual other | Aiello 2021 (null) vs Li 2023 (null) on contextual other | agreement (minor) | | agreement | 1 | Fang 2021 | Feng 2022 | contextual other | Fang 2021 (null) vs Feng 2022 (null) on contextual other | agreement (minor) | | agreement | 1 | Fang 2021 | Croize-Pourcelet 2022 | contextual other | Fang 2021 (null) vs Croize-Pourcelet 2022 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Fang 2021 | Cai 2022 | contextual other | Fang 2021 (null) vs Cai 2022 (unclear) on contextual other | null vs positive (notable) | | disagreement | 4 | Fang 2021 | Mandala 2023 | contextual other | Fang 2021 (null) vs Mandala 2023 (mixed) on contextual other | disagreement (load-bearing) | | agreement | 1 | Fang 2021 | Li 2023 | contextual other | Fang 2021 (null) vs Li 2023 (null) on contextual other | agreement (minor) | | agreement | 1 | Feng 2022 | Croize-Pourcelet 2022 | contextual other | Feng 2022 (null) vs Croize-Pourcelet 2022 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Feng 2022 | Cai 2022 | contextual other | Feng 2022 (null) vs Cai 2022 (unclear) on contextual other | null vs positive (notable) | | disagreement | 4 | Feng 2022 | Mandala 2023 | contextual other | Feng 2022 (null) vs Mandala 2023 (mixed) on contextual other | disagreement (load-bearing) | | agreement | 1 | Feng 2022 | Li 2023 | contextual other | Feng 2022 (null) vs Li 2023 (null) on contextual other | agreement (minor) | | null vs positive | 3 | Croize-Pourcelet 2022 | Cai 2022 | contextual other | Croize-Pourcelet 2022 (null) vs Cai 2022 (unclear) on contextual other | null vs positive (notable) | | disagreement | 4 | Croize-Pourcelet 2022 | Mandala 2023 | contextual other | Croize-Pourcelet 2022 (null) vs Mandala 2023 (mixed) on contextual other | disagreement (load-bearing) | | agreement | 1 | Croize-Pourcelet 2022 | Li 2023 | contextual other | Croize-Pourcelet 2022 (null) vs Li 2023 (null) on contextual other | agreement (minor) | | disagreement | 4 | Cai 2022 | Mandala 2023 | contextual other | Cai 2022 (unclear) vs Mandala 2023 (mixed) on contextual other | disagreement (load-bearing) | | null vs positive | 3 | Cai 2022 | Li 2023 | contextual other | Cai 2022 (unclear) vs Li 2023 (null) on contextual other | null vs positive (notable) | | disagreement | 4 | Mandala 2023 | Li 2023 | contextual other | Mandala 2023 (mixed) vs Li 2023 (null) on contextual other | disagreement (load-bearing) |

Table 4 (supplemental): Design-Level Evidence Weighting Heuristic

Per-domain grades are derived from each study's evidence tier (A1/A2/B1/B2/C1/C2) — they capture design-level limitations, NOT a formal per-paper risk-of-bias assessment from the source text. Domains follow design-family categories for randomized, observational, animal, and systematic-review evidence; n/a indicates the domain is not meaningful for that design (e.g. blinding for an observational cohort). The Weight in synthesis column is the qualitative weighting the synthesis applies to each source — derived from tier × directness × overall RoB.

CitationTierToolAllocationBlindingAttritionOutcome measurementReportingConfounding controlGeneralizabilityOverall RoBWeight in synthesisEffect direction notes
Beker 2020B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)negative effect — see Tables 1/2
Yamamoto 2025B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)primary endpoint did not reach significance
Evans 2014B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)signed claims without significance signal
Pineiro-Fernandez 2025B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)signed claims without significance signal
Gimeno-Miguel 2019B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)primary endpoint did not reach significance
Beker 2019B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)primary endpoint did not reach significance
Murata 2023B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)primary endpoint did not reach significance
Suh 2025B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)primary endpoint did not reach significance
Wang 2019B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)signed claims without significance signal
Hazra 2015B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)primary endpoint did not reach significance
Biagi 2010B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)positive effect — see Tables 1/2
Dai 2024B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)primary endpoint did not reach significance
Garcia-Vivanco 2025B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)primary endpoint did not reach significance
Cai 2016B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)primary endpoint did not reach significance
Sebastiani 2021B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)primary endpoint did not reach significance
Fang 2021C1SYRCLE (animal)lown/alowmoderatemoderaten/ahighlowhypothesis-generating (preclinical mechanism)primary endpoint did not reach significance
Lastoria 2023B1AMSTAR-2 (review)unclearunclearunclearunclearmoderatemoderatemoderateunclearsupporting (synthesis evidence)signed claims without significance signal
Jang 2023B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)primary endpoint did not reach significance
Gu 2015B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)signed claims without significance signal
Cai 2022B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)signed claims without significance signal
Lindberg 2025B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)signed claims without significance signal
Sasaki 2023B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)signed claims without significance signal
Arnold 2010B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)signed claims without significance signal
Vitale 2012B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)primary endpoint did not reach significance
Feng 2022B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)primary endpoint did not reach significance
MarcosPerez 2025B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)primary endpoint did not reach significance
Garagnani 2013B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)primary endpoint did not reach significance
Collino 2013B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)primary endpoint did not reach significance
Li 2023B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)primary endpoint did not reach significance
Santos-Lozano 2020B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)primary endpoint did not reach significance
Mandala 2023B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)internal contradiction across endpoints
Gavrilov 2011B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)primary endpoint did not reach significance
Aiello 2021B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)primary endpoint did not reach significance
Ruiz 2019B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)primary endpoint did not reach significance
Marcon 2020B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)positive effect — see Tables 1/2
Croize-Pourcelet 2022B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)primary endpoint did not reach significance
Aliberti 2024B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)signed claims without significance signal
Ono 2024B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)primary endpoint did not reach significance
Espinosa 2025B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)primary endpoint did not reach significance
Najafi 2024B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)primary endpoint did not reach significance
Aliberti 2025C1SYRCLE (animal)lown/alowmoderatemoderaten/ahighlowhypothesis-generating (preclinical mechanism)primary endpoint did not reach significance
Balistreri 2012B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)primary endpoint did not reach significance
Wu 2019B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)primary endpoint did not reach significance
Ungvari 2023C1SYRCLE (animal)lown/alowmoderatemoderaten/ahighlowhypothesis-generating (preclinical mechanism)primary endpoint did not reach significance
Aliberti 2025bB2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)primary endpoint did not reach significance
Aliberti 2025cB2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)primary endpoint did not reach significance
Govindaraju 2015B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)primary endpoint did not reach significance
Santoro 2017B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)primary endpoint did not reach significance
Marston 2021B2ROBINS-In/an/amoderatemoderatemoderatehighmoderatemoderatecontextual (observational signal)primary endpoint did not reach significance
Mazzola 2016B1AMSTAR-2 (review)unclearunclearunclearunclearmoderatemoderatemoderateunclearsupporting (synthesis evidence)primary endpoint did not reach significance

Table 5 (supplemental): Per-Paper Numeric Index

Top-N quantitative claims per paper — the underlying corpus numerics that power Q2 trace and Q9 density. One row per (paper × claim) tuple, prioritised by claim type (p-value > percentage > ratio > unit-value).

CitationSectionTypeValueUnits
Evans 2014discussionpercentage17.7%%
Pineiro-Fernandez 2025resultspercentage15%%
Pineiro-Fernandez 2025resultspercentage95%%
Lastoria 2023introductionunit value80 yearsyears
Cai 2022discussionp-valueP < 0.05
Lindberg 2025discussionpercentage35%%
Lindberg 2025discussionpercentage40%%
Mazzola 2016abstractunit value3 monthsmonths

Methods

Review type and protocol

This manuscript is reported as a Evidence brief. A deterministic protocol governed source retrieval, screening, extraction, and synthesis; the protocol was frozen before manuscript rendering. The full audit trail is in the supplementary methods_pack.json and the timestamped submission directory synthesis-blue_zones_diet_lifestyle-v06-DAILY-2026-05-28T07-25-34Z.

Information sources

Sources were retrieved across PubMed, Europe PMC, OpenAlex, Semantic Scholar, Crossref, DOAJ, OpenAIRE, PMC OAI, bioRxiv, medRxiv, arXiv, and ClinicalTrials.gov. Retrieval window: 2026-05-28.

Search strategy

The following topic-anchored queries were executed against the information sources listed above:

  • blue zones diet lifestyle AND aging AND human
  • blue zones diet lifestyle AND older adults
  • blue zones diet lifestyle AND randomized controlled trial
  • Blue Zones AND aging AND human
  • Blue Zones AND older adults
  • Blue Zones AND randomized controlled trial
  • longevity diet AND aging AND human
  • longevity diet AND older adults
  • longevity diet AND randomized controlled trial
  • lifestyle longevity AND aging AND human

Eligibility criteria

  • Sources whose primary content addresses blue zones diet lifestyle.
  • Sources with extractable quantitative or qualitative findings.
  • Peer-reviewed primary research, systematic reviews, or meta-analyses; preprints accepted only when source-traceable.
  • Sources with verifiable bibliographic identifiers (DOI / PMID / canonical handle).

Selection of sources of evidence

The synthesis did not begin from an unfiltered database export. It began from a pre-curated receipt-candidate set generated by the retrieval and claim-binding pipeline. Of 183 records in the receipt-candidate union, 63 were classified as source candidates and 50 were admitted as traceable synthesis sources. No additional records were excluded after final source admission.

source admission funnel

Admission bucketn
Receipt candidate union183
Classified source candidates63
No extractable claims29
None-only claim binding7
Partial/none-only claim binding56
Partial-only candidates22
Strict high-confidence sources6
Admitted final sources50

Exclusion reasons

  • Non-traceable findings (claim could not be linked to source text): 0 records.
  • Wrong population / off-topic sources excluded at screening.
  • Duplicate records deduplicated by DOI / PMID before screening.

Data items

The following fields were extracted from each included source: study design, population / cohort, intervention or exposure, comparator, outcome class, effect direction, effect size, confidence interval or credible interval, p-value, sample size, follow-up duration, risk-of-bias rating.

Risk-of-bias appraisal

Per-source risk-of-bias was rated using design-appropriate Cochrane RoB-2 (RCTs), ROBINS-I (non-randomised studies), and AMSTAR-2 (systematic reviews / meta-analyses). Ratings recorded in risk_of_bias.json.

Synthesis approach

Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, deficiency prevalence, frailty, longevity, mortality and survival, skeletal, fracture, and bone); within-class agreement, disagreement, and directness gaps surfaced explicitly. Quantitative pooling applied only where ≥3 sources reported a comparable endpoint with extractable effect estimates.

AI-use disclosure

Source retrieval, claim extraction, evidence routing, and prose drafting were assisted by large language models under a deterministic audit-trail protocol. Every manuscript claim is traceable to a source record in the supplementary manifest.json. Final eligibility and interpretation decisions are author-verified.

Accountability

Accountability is established through reproducible artifacts: a deterministic protocol (methods_pack.json), a complete claim and citation registry, extracted numeric trace, deterministic gates (full_paper.journal_surface.json, pre_submit_gate.json, artifact_consistency.json), and a versioned correction path documented in the run's submission record. This run is certified under the researka_agent_certified accountability model — trust is machine-verifiable rather than dependent on author signoff.

References

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  • Yamamoto 2025. Functional outcomes following injury in centenarians: a nationwide retrospective observational study. World Journal of Emergency Surgery : WJES, 2025. DOI: 10.1186/s13017-025-00595-6. PMID: 40186255.
  • Evans 2014. Place and Cause of Death in Centenarians: A Population-Based Observational Study in England, 2001 to 2010. PLoS Medicine, 2014. DOI: 10.1371/journal.pmed.1001653. PMID: 24892645.
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  • Santos-Lozano 2020. Successful aging: insights from proteome analyses of healthy centenarians. Aging (Albany NY), 2020. DOI: 10.18632/aging.102826. PMID: 32100723.
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  • Ruiz 2019. Dosage form suitability in vulnerable populations: A focus on paracetamol acceptability from infants to centenarians. PLoS ONE, 2019. DOI: 10.1371/journal.pone.0221261. PMID: 31430323.
  • Marcon 2020. COVID-19 mortality in Lombardy: the vulnerability of the oldest old and the resilience of male centenarians. Aging (Albany NY), 2020. DOI: 10.18632/aging.103872. PMID: 32788424.
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Proof Trail

Decision: AcceptLiving evidence briefGate failures: 0

Topic: research

Author: Dominic Lynch

Author ORCID: 0009-0005-4286-8363

Institution: not supplied

ROR: not supplied

RAiD: not supplied

OSF DOI: 10.17605/OSF.IO/BEX3H

AI co-writer: agent-v3-full-paper

Reviewer: reviewer-panel

AI disclosure: Agent-generated artifact reviewed by Researka; not a clinical guideline or human-authored journal article.

Integrity check: not recorded

Published: May 28, 2026

Provenance chain: Available → View

SHA-256: sha256:839f9db77a9...

Publication ID: 760aab4f-9e69-4800...

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