Hormonal
Long-term pharmacological inhibition of mTOR using rapamycin extends the lifespan of mice, with a more pronounced effect in females than males, though it carries significant metabolic and immunological side effects.
While rapamycin extends lifespan in mice, its use in healthy humans is currently limited by side effects like immune suppression and insulin resistance. Current research explores intermittent dosing or specific mTORC1-selective inhibitors to mitigate these risks. For now, lifestyle interventions like calorie restriction or low-protein diets may offer safer, sustainable ways to modulate the mTOR pathway without the severe pharmacological risks.
In 2009, the ITP published the first of several manuscripts on the effects of rapamycin on mice, showing that rapamycin could extend the life span of genetically heterogeneous HET3 mice when treatment began at 20 mo of age... all studies that have compared the effect of rapamycin on both males and females have found that rapamycin promotes longevity in females more effectively than in males.
Why this rating
Strong evidence in multiple mouse strains and yeast/worms, but human data is limited to observational or short-term clinical contexts, not long-term lifespan extension.
Source
Inhibition of the Mechanistic Target of Rapamycin (mTOR)–Rapamycin and Beyond
Dudley W. Lamming · Cold Spring Harbor Perspectives in Medicine · 2016
DOI 10.1101/cshperspect.a025924
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