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At non\u2010immunosuppressive 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\u2010organism ageing, we tested whether mTOR inhibition enhances genome stability. In human T cells exposed to acute genotoxic stress, we found that rapamycin and other mTOR inhibitors suppressed senescence not by slowing protein synthesis, halting cell division, or stimulating autophagy, but by directly reducing DNA lesional burden and improving cell survival. Ex\u00a0vivo analysis of aged immune cells from healthy donors revealed a stark enrichment of markers for DNA damage, senescence, and mTORC hyperactivation, suggesting that human immune ageing may be amenable to intervention by low\u2010dose mTOR inhibition. To test this in\u00a0vivo, we conducted a placebo\u2010controlled experimental medicine study in older adults administered with low\u2010dose rapamycin. p21, a marker of DNA damage\u2010induced senescence, was significantly reduced in immune cells from the rapamycin compared to placebo group. These findings reveal a previously unrecognised role for mTOR inhibition: direct genoprotection. This mechanism may help explain rapamycin's exceptional geroprotective profile and opens new avenues for its use in contexts where genome instability drives pathology, ranging from healthy ageing, clinical radiation exposure and even the hazards of cosmic radiation in space travel.<\/jats:p>","DOI":"10.1111\/acel.70364","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T14:50:21Z","timestamp":1768229421000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Rapamycin Exerts Its Geroprotective Effects in the Ageing Human Immune System by Enhancing Resilience Against\n                    <scp>DNA<\/scp>\n                    Damage"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1322-2027","authenticated-orcid":false,"given":"Loren","family":"Kell","sequence":"first","affiliation":[{"name":"Department of Biochemistry University of Oxford  Oxford 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