The interventions with the most robust clinical evidence for longevity are not supplements — they are behaviors. Regular physical activity has the strongest evidence base of any longevity intervention, with dose-response data showing cardiovascular and all-cause mortality reduction that continues with increasing volume up to very high levels. Strength training specifically preserves muscle mass (sarcopenia), functional independence, metabolic rate, and bone density — all major determinants of quality of life in the final decades.
Dietary patterns associated with longevity in observational data — Mediterranean, DASH, Blue Zone diets — share common features: high vegetable and fruit intake, whole grains, legumes, olive oil or fish as primary fat sources, and low ultra-processed food intake. The Mediterranean diet has the strongest intervention trial data for cardiovascular outcomes (PREDIMED trial). Caloric restriction extends lifespan robustly in animal models — evidence in humans is mechanistically supportive but not definitively established for clinical longevity outcomes.
Sleep is increasingly recognized as a longevity determinant. Habitual short sleep (<6 hours) is associated with accelerated biological aging in multiple biomarker studies, increased all-cause mortality, and substantially elevated cardiometabolic and cancer risk. The relationship appears U-shaped — both short and long sleep duration are associated with excess mortality — suggesting optimal sleep of 7–8 hours for most adults.
The most hyped longevity supplements — NMN, resveratrol, rapamycin, metformin for longevity (not diabetes) — have mechanistic rationale based on mTOR, AMPK, and sirtuin pathways but lack robust clinical outcomes data in humans. NAD+ precursors (NMN, NR) have demonstrated safety and NAD+ elevation in humans but have not shown clinical longevity endpoints. Metformin's TAME trial (Targeting Aging with Metformin) is underway — the first large randomized trial targeting biological aging. Results are expected in the late 2020s.