Research
Hormonal
Chronic inhibition of mTORC2 by rapamycin causes metabolic dysfunction (glucose intolerance, insulin resistance) and immunosuppression, acting as the primary barrier to its use as an anti-aging therapy.
Chronic daily use of rapamycin is likely unsafe for long-term anti-aging due to the risk of diabetes and immune suppression caused by mTORC2 inhibition. This mechanism explains why 'more is not better' with this drug.
StrongRefutesVERY_HIGH confidence
It has now been conclusively demonstrated that disruption of mTORC2 contributes to several of these effects, particularly glucose intolerance, diabetes, and immunosuppression.
Why this rating
Supported by genetic models (Rictor deletion) and pharmacological studies across multiple tissues (liver, muscle, beta cells).
Source
Rapamycin: An InhibiTOR of Aging Emerges From the Soil of Easter Island
Sebastian I. Arriola Apelo et al. · The Journals of Gerontology Series A · 2016
DOI 10.1093/gerona/glw090
narrative_reviewCited 233×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
More from this paper
- Intermittent administration of rapamycin (e.g., 2 mg/kg every 5 days) extends lifespan in mice while minimizing metabolic and immunological side effects associated with chronic dosing.Good
- Rapamycin exhibits sexual dimorphism in efficacy, extending lifespan significantly more in female mice than in male mice.Good
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