These drugs require a prescription from a physician following individual assessment and discussion of the potential risks and benefits of their use:
Metformin — (for non-diabetics) 1.5g to 2g daily as extended release. Metformin up-regulates 5’ AMP-activated protein kinase (AMPK), an exercise-mimetic hormone with numerous beneficial effects including regulation of lipid metabolism. It also has anti-inflammatory, antioxidant, cardioprotective, metabolic, neuroprotective, anti-cancer and anti-microbial benefits. It prolongs lifespan in animal studies and observational data suggested a similar effect in humans. More conclusive human outcome studies are ongoing, one of which has already shown anti-ageing transcriptional changes. Whether metformin can extend health-span and lifespan in otherwise healthy individuals remains controversial, but there is convincing evidence of benefit when used in diabetics, patients with cardiovascular disease, those with cognitive decline and cancer — the sicker a patient the greater the potential benefit.
Sirolimus — 6mg once weekly. Metformin stimulates AMPK which has a weak inhibitory effect on the growth regulator of mammalian target of rapamycin (mTOR). Sirolimus blocks mTOR far more effectively and is perhaps the most effective and science-backed anti-ageing medicine presently available (2023).
mTOR controls cell growth and metabolism, so it is essential for youthful growth and health. In youthful organisms mTOR is released in a pulsatile fashion in response to nutrient intake, growth factors and stress-signalling. With ageing mTOR levels rise and stay elevated chronically, no longer appearing in brief pulses and returning to low baseline levels. Chronically elevated mTOR appears to be a crucial factor behind a lot of age-related dysfunction and has been shown to promote cancer cell proliferation and accelerated tumour progression. Suppression of mTOR using sirolimus (originally called Rapamycin) has been shown to robustly extend health-span and lifespan in every organism tested to date. Preliminary human studies continue to suggest health-span and lifespan benefits, but trials are either ongoing or recruiting — human outcome data will be available in the coming years.
If used daily sirolimus can have immunosuppressive properties, so a single dose of 6mg is given once weekly. This once-weekly pulse suppresses mTOR1 (which confers the longevity benefits) and not mTOR2 (inhibition causes insulin resistance). Despite this there is still some risk of immunosuppression with once-weekly sirolimus so careful monitoring is necessary. There is also little long-term data identifying other potential downsides of this regimen so the risks of long-term once-weekly use remain unclear.
In summary, there are potential anti-ageing and anti-cancer benefits with sirolimus, but the long-term risk is yet to be determined. Each individual considering this therapy (FDA approved for other indications) will be taking a leap of faith in the absence of robust human trial data.
Other drugs — Several other prescription medications can be given for potential health-span and lifespan benefits. Some of these have been mentioned before, for example ACE-i, ARBs and Eplerenone for effects on angiotensin and aldosterone, while other drugs are nuanced and require individual discussion.