Research Synthesis: Rapamycin Effects — full paper

Researka accepted publication: 1ece772b-d3e4-4ad0-b090-ac7e9ea4a1d6 Source submission: 5b531a37-a8e4-47cd-b276-14815f69553f Evidence-honesty note: 22/36 retained sources are coded as null or no extracted directional signal; this corpus is non-supportive for clinical efficacy claims and hypothesis-generating only. 35/36 retained sources are indirect, review-level, adjacent, or mechanistic and are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims. Rapamycin, an mTOR inhibitor, has emerged as a candidate geroprotector, but its translation from preclinical lifespan extension to human healthspan benefits remains contentious. This structured evidence synthesis, employing AI-assisted screening and critical appraisal with a full audit trail, integrated 36 reference papers to map rapamycin's effects across longevity, healthspan, safety, and disease-specific outcomes. Meta-analysis across vertebrates indicates rapamycin, unlike metformin, mirrors dietary restriction-driven lifespan extension, with a significant combined effect (IvimeyCook 2025; Liao 2025). The immune-modulatory profile is complex, with evidence of both suppressed inflammation (Ge 2023) and enhanced vaccine-induced memory T-cell responses (Withers 2025), highlighting context-dependent effects. Topical application showed a significant reduction in skin senescence markers (Chung 2019), suggesting route-specific efficacy.