# Rapamycin and mTOR inhibition for ageing

Source: https://onco.cc/technologies/rejuv-frontier-rapamycin-ageing/  
OnCo record `rejuv-frontier-rapamycin-ageing` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Rapamycin extends life in every species it has been properly tested in, which is why people take it off-label. In humans there are two randomised results worth knowing: a related drug improved the flu vaccine response in older people by about a fifth, and a year of low-dose rapamycin in healthy adults did not change its primary endpoint. That is the whole of it.

## Summary

Rapamycin (sirolimus) and its analogues inhibit mTOR, the pathway whose suppression extends lifespan in yeast, worms, flies and mice. Two human randomised trials matter here. In the first, RAD001 (everolimus) given to elderly volunteers before influenza vaccination improved the antibody response by about 20 per cent at reasonably tolerated doses and reduced the proportion of PD-1-expressing CD4 and CD8 T cells. In the second, the PEARL trial, 48 weeks of intermittent rapamycin at 5 mg or 10 mg weekly in healthy normative-ageing adults left the primary endpoint, visceral adiposity by DXA, unchanged (P = 0.942). Adverse and serious adverse events were similar across groups. Lean tissue mass and self-reported pain improved in women on 10 mg, and emotional wellbeing and general health improved on 5 mg; these are secondary and self-reported outcomes in a decentralised trial.

In oncology mTOR inhibitors are approved cancer drugs with a known profile: stomatitis, non-infectious pneumonitis, hyperglycaemia, hyperlipidaemia and immunosuppression. They are used after transplant precisely because they suppress immunity, which is not an obvious thing to add to someone whose immune system is still reconstituting after chemotherapy. Compounded rapamycin sold through longevity clinics is not the same supply chain as the licensed product.

There is no trial of rapamycin in cancer survivors for ageing outcomes, and no guideline anywhere recommends it for that purpose.

## Fields

- Kind: Technology
- Status: phase-2
- Last checked: 2026-10-02
- Tags: rejuvenation; survivorship; evidence:insufficient; repurposing
- Principle: mTORC1 integrates nutrient and growth signals and drives protein synthesis while suppressing autophagy. Partial, intermittent inhibition is thought to restore autophagic clearance and reduce the anabolic load that accumulates with age; the immune effect seen with everolimus is attributed to reduced T-cell exhaustion markers.
- Strengths: The most reproducible lifespan effect in animal models of any drug; One randomised human trial showing improved vaccine response in older people; A 48-week randomised safety trial found no excess of adverse events at low intermittent doses
- Limitations: The 48-week randomised trial missed its primary endpoint; Immunosuppression, stomatitis, pneumonitis, hyperglycaemia and hyperlipidaemia are established effects of the drug class; No trial in cancer survivors and no guideline support for this use; Compounded supply sold by longevity clinics is outside the licensed product's quality controls

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Sirolimus
- Mannick et al., mTOR inhibition improves immune function in the elderly (Sci Transl Med 2014): https://doi.org/10.1126/scitranslmed.3009892
- Zalzala et al., Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results (Aging 2025): https://doi.org/10.18632/aging.206235

## Connected records

- technologies: [Rebuilding the immune system after treatment](https://onco.cc/technologies/rejuv-frontier-immune-reconstitution/), [Survivorship care and late-effects surveillance](https://onco.cc/technologies/survivorship-care-plan/), [What actually works after treatment](https://onco.cc/technologies/rejuv-frontier-what-works/)
- fronts: [Recovery & Rejuvenation](https://onco.cc/fronts/rejuvenation/), [Supportive Care & Survivorship](https://onco.cc/fronts/supportive-care/)
- drugs: [Everolimus](https://onco.cc/drugs/everolimus/), [Sirolimus](https://onco.cc/drugs/sirolimus/)
- terms: [Late effects and survivorship toxicity](https://onco.cc/terms/late-effects/)
- bottlenecks: [Survivorship and late effects are neglected](https://onco.cc/bottlenecks/b-survivorship/)

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