Guide
The current state of human longevity trials
9 min read · last reviewed 22 August 2026
For a field with this much marketing, the list of completed human trials with ageing-relevant endpoints is strikingly short. Here is the honest inventory — what has reported, what it found, and what remains genuinely open.
The trials that reported null
The biggest and cleanest results in this field are negative, and they are underrated. D-Health randomised over 21,000 older adults and found vitamin D did not reduce mortality. VITAL randomised over 25,000 adults and found a gram of omega-3 daily prevented neither cardiovascular disease nor cancer. TREAT found the most popular fasting schedule produced no weight-loss advantage over ordinary meal timing. Null results from large well-run trials are how a field learns; they deserve the prominence usually reserved for positive ones.
The trials that moved things forward
CALERIE showed two years of sustained calorie restriction is feasible for carefully selected adults and improves cardiometabolic risk factors — the closest thing to a flagship human trial of a core ageing intervention. REDUCE-IT showed a targeted intervention in a defined high-risk group can deliver hard-outcome benefits, and is a model of what specific looks like against the field's habit of universal claims.
The cautionary arc: mTOR and immunity
Low-dose mTOR inhibition produced two of the most exciting randomised results of the 2010s — improved vaccine response in 2014, fewer reported infections in 2018. The confirmatory phase 3 then failed, and the programme was discontinued. It remains the field's best modern lesson in why replication is a requirement, not a courtesy. Meanwhile the PEARL trial has since reported one year of intermittent low-dose rapamycin as generally tolerable in healthy adults — reopening the question at a smaller scale.
What the field is waiting for
The TAME trial — metformin in thousands of older adults without diabetes, with a composite of age-related diseases as the endpoint — has been the field's promised centrepiece for years and has not reported. Senolytic trials are early. Live registrations across these areas can be tracked on our trials page, drawn directly from ClinicalTrials.gov.
Sources
- [1]D-Health: vitamin D and all-cause mortality (Lancet Diabetes Endocrinol, 2022). PMID 35026158
- [2]VITAL: marine n-3 fatty acids (NEJM, 2019). PMID 30415637
- [3]CALERIE: 2 years of calorie restriction and cardiometabolic risk (Lancet Diabetes Endocrinol, 2019). PMID 31303390
- [4]TREAT: time-restricted eating and weight loss (JAMA Internal Medicine, 2020). PMID 32986097
- [5]mTOR inhibition phase 2b/3 (Lancet Healthy Longevity, 2021). PMID 33977284
- [6]PEARL: one-year rapamycin trial (Aging, 2025). PMID 40188830