CLAIM CARD
Tensions within the corpus emerge prominently from studies reporting adverse or null effects that contrast with the predominantly positive preclinical signal. Translational relevance to humans remains uncertain. Dou 2017 showed that even short-term 2-week rapamycin treatment caused disturbances in ovarian function alongside beneficial effects on ovarian lifespan (P < 0.01 for both beneficial and adverse endpoints). Minton 2024 further reported that mTORC1 inhibition by rapamycin resulted in feedback activation of Akt and aggravated hallmarks of osteoarthritis in female mice and non-human primates. These adverse-signal studies, particularly Fischer 2015, Geissler 2015, and Minton 2024, challenge the assumption that rapamycin effects are uniformly beneficial across tissues and species (Fischer 2015; Geissler 2015; Dou 2017; Minton 2024).
Evidence grade: exploratory
Contradiction status: none
Publication: f02d4a53-03e5-47ed-9876-75a416e3bd24
Provenance: Derivation Web chain
Citation Support
source_1Moel 2025source_2Gkioni 2025source_3Smiaek 2023source_4Willows 2023source_5Harinath 2025