Longevity Interventions: What Human Evidence Exists

Habits

Physical activity: established as a health habit. A 2023 meta-analysis pooled 94 cohorts with more than 30 million participants. People with higher activity had lower risk of death and disease. At about the level of 150 minutes a week of moderate-to-vigorous aerobic activity, the relative risk of all-cause death was 0.69 compared with no activity, with smaller added differences above that level. [1] These are observational studies, so they show association rather than proof of cause, but the pattern is consistent. The National Institute on Aging also lists staying active, healthy food choices, enough sleep, limited alcohol and managing health care as steps within reach. [2] See Physical Activity and Longevity and Healthy Aging.

Calorie restriction: promising but limited. In the CALERIE trial, 218 adults without obesity, aged 21 to 51, were randomized to aim for 25% calorie restriction or usual eating for two years. They reached about 12% restriction and kept off about 10% of their weight; the report said quality of life was not harmed. [3] A later analysis found a small slowing of one DNA methylation "pace of aging" score (DunedinPACE) but no significant change in two other clocks, and said a conclusive test needs long follow-up on chronic disease and death. [4] That is a change in markers, not proof of longer life. See Calorie Restriction and Aging Research.

Supplements

Antioxidant vitamins: no good evidence of benefit, and evidence of harm for some. A meta-analysis of 68 randomized trials (232,606 participants) found no significant effect on death when all trials were pooled. In the 47 lower-bias trials, supplements slightly increased mortality (relative risk 1.05), and beta carotene, vitamin A and vitamin E may increase mortality; vitamin C and selenium showed no significant effect. [5] This analysis searched studies published by October 2005, so newer trials are not included. See Antioxidant Supplements and Aging.

NAD+ precursors (NMN, nicotinamide riboside): promising but limited. A 2023 review found these supplements were safe and tolerable in the studies done and raised NAD+ and related molecules, but said the clinical evidence that raising NAD+ improves physiological function is unclear, and small samples limit interpretation. [6] In the National Institute on Aging mouse program, nicotinamide riboside did not extend lifespan. [7] See NAD+, NMN and Nicotinamide Riboside.

Vitamin D, omega-3 and exercise: biomarker signal only. In a post hoc analysis of 777 DO-HEALTH participants over 3 years, omega-3 alone slowed three of four DNA methylation clocks slightly, with effects of about 3 to 4 months in clock units. [8] It is a change in a biomarker, in one analysis chosen after the trial, not a health outcome. Label: insufficient evidence for longer or healthier life.

Prescription medicines under study

Rapamycin, metformin and senolytics are covered on Experimental Longevity Compounds. In short, mouse lifespan gains exist for rapamycin, [9] but a 48-week human rapamycin trial did not change its main outcome, [10] and a 2025 review described growing uncertainty about metformin. [11] Aspirin shows what a proper aging-outcome trial can find: in 19,114 healthy older adults, aspirin did not prolong disability-free survival and caused more major bleeding. [12]

Summary table