Rapamycin / sirolimus (off-label, low-dose intermittent)

The lifespan case rests on animal data, not humans. Rodent evidence is genuinely robust and reproducible, which is why rapamycin is taken seriously by ageing biologists rather than dismissed. Human evidence is far thinner. A 2025 review in Aging identified fewer than a dozen trials of low-dose rapamycin or analogues in healthy participants, and concluded that human data "has yet to establish that rapamycin, or its analogues, is an effective seno-therapeutic to delay aging in healthy older adults." The human trials that exist are small, short, and measure surrogate endpoints rather than ageing outcomes: Kraig 2018 dosed 25 adults aged 70 to 95 with 1 mg/day for 8 weeks; Mannick's work used the analogue everolimus and RTB101 for immune and respiratory-infection endpoints, and the phase 3 results failed to replicate the earlier phase 2b signal. Kaeberlein's 333-user cohort is observational and unblinded, so it cannot support causal claims. No human trial has demonstrated extended healthspan or lifespan. Documented adverse findings in these studies include raised triglycerides and HbA1c, reduced plasma albumin and haemoglobin, elevated TNF-alpha, oral ulcers, and increased anxiety at some doses, so this is not a low-consequence intervention and it carries genuine immunosuppression risk requiring baseline and ongoing bloodwork. Grading this as preclinical rather than clinical is deliberate: human RCTs exist, but none establish the healthspan outcome the protocol is sold on.

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