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Mechanistically, preclinical data from Wang 2017b demonstrate that rapamycin inhibits the secretory phenotype of senescent cells via an Nrf2-independent mechanism, with senescent fibroblasts showing decreased Nrf2 protein (~65%) and mRNA levels (~45%) relative to presenescent counterparts. Leontieva 2016 describes gerosuppression by pan-mTOR inhibitors, showing that cells treated for 4 days re-proliferated as effectively in drug-free medium, suggesting a reversible senomorphic effect. Leontieva 2011 further characterizes how rapamycin shifts cells from senescence to quiescence rather than eliminating them, a mechanism that may underlie the immunomodulatory profile observed in clinical studies.

Evidence grade: exploratory

Contradiction status: none

Publication: f02d4a53-03e5-47ed-9876-75a416e3bd24

Provenance: Derivation Web chain

Citation Support

  • source_1 Moel 2025
  • source_2 Gkioni 2025
  • source_3 Smiaek 2023
  • source_4 Willows 2023
  • source_5 Harinath 2025

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