Rapamycin Exerts Its Geroprotective Effects in the Ageing Human Immune System by Enhancing Resilience Against DNA Damage

Kell L, Jones EJ, Gharahdaghi N, Wilkinson DJ, Smith K, Atherton PJ, Simon AK, Cox LS, Alsaleh G · 2026 · Aging Cell · Atlas ID KEL2026

What this study shows

Identifies a previously unrecognized geroprotective mechanism for rapamycin: direct genoprotection. In human T cells exposed to acute genotoxic stress, rapamycin and other mTOR inhibitors suppressed senescence not by slowing protein synthesis, halting cell division, or stimulating autophagy, but by directly reducing DNA lesion burden and improving cell survival. Ex vivo aged human immune cells showed elevated DNA damage, senescence and mTORC-hyperactivation markers. In a placebo-controlled experimental medicine study, low-dose rapamycin significantly reduced p21 (a DNA-damage-induced senescence marker) in immune cells of older adults versus placebo.

Abstract

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mTOR inhibitors such as rapamycin are among the most robust life-extending interventions known, yet the mechanisms underlying their geroprotective effects in humans remain incompletely understood. At non-immunosuppressive doses, these drugs are senomorphic, that is, they mitigate cellular senescence, but whether they protect genome stability itself has been unclear. Given that DNA damage is a major driver of immune ageing, and immune decline accelerates whole-organism ageing, we tested whether mTOR inhibition enhances genome stability.

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At a glance

Evidence type	H Human study Marked H because it is direct evidence from a human clinical trial or human cohort; the code names the kind of study, not its quality -- a small, well-run trial is still H.
Study type	2 - Human Clinical Trial
Model system	Human T cells (ex vivo, genotoxic stress); ex vivo aged human immune cells; placebo-controlled experimental medicine study in older adults (low-dose oral rapamycin, in vivo)
Journal	Aging Cell
Year	2026
Peer reviewed	Yes
Record last updated	2026-09-23
Source	DOI 10.1111/acel.70364 · PMID 41524558 · Free full text (PMC12794675)

Cite this paper

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Kell, L., Jones, E. J., Gharahdaghi, N., Wilkinson, D. J., Smith, K., Atherton, P. J., Simon, A. K., Cox, L. S., & Alsaleh, G. (2026). Rapamycin Exerts Its Geroprotective Effects in the Ageing Human Immune System by Enhancing Resilience Against DNA Damage. Aging Cell. https://doi.org/10.1111/acel.70364

@article{KEL2026,
  author       = {Kell, L. and Jones, E. J. and Gharahdaghi, N. and Wilkinson, D. J. and Smith, K. and Atherton, P. J. and Simon, A. K. and Cox, L. S. and Alsaleh, G.},
  title        = {{Rapamycin Exerts Its Geroprotective Effects in the Ageing Human Immune System by Enhancing Resilience Against DNA Damage}},
  journal      = {Aging Cell},
  year         = {2026},
  doi          = {10.1111/acel.70364},
  note         = {PMID: 41524558},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record KEL2026) [Data set]. https://mtor-atlas.org/study/KEL2026/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_KEL2026,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record KEL2026},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/KEL2026/},
  doi          = {10.5281/zenodo.22059963}
}