Measurable Longevity Interventions
Interventions tested against a measured biological-age clock
These are lifestyle and protocol interventions that have been tested against an epigenetic clock A test that estimates biological age from chemical marks on DNA (DNA methylation). in human participants. Each one carries two separate grades. The Health grade reflects the strength of the human evidence that the intervention improves health and longevity outcomes. The Clock grade reflects only the strength of the human evidence that it moves a biological-age clock. The two often disagree, and where they do, this page says so plainly. Ordered below by the strength and size of the clock evidence, strongest first.
How to read these grades
Health grade. Confidence, from human trials, that the intervention improves real health and longevity outcomes. This grade is about outcomes rather than markers.
Clock grade. Confidence, from human trials, that the intervention lowers a measured epigenetic age. A clock is a surrogate marker A lab value or measurement used in place of the outcome that matters, such as LDL cholesterol standing in for heart attacks. Moving a surrogate does not always move the outcome., not a measure of remaining lifespan.
Clock effect. The reported reduction in biological age, shown with its honest caveat. A larger number from a weaker study does not outrank a smaller number from a stronger one.
Tier. A rough grouping by how direct and how demanding the protocol is, not a ranking of value. A Tier 4 long-term pattern can carry stronger health evidence than a Tier 2 protocol.
One person, one measurement
Every clock effect on this page is a group result: an average across the people in a trial. A single person's before-and-after reading is a different measurement, and it carries an error of its own.
That error is large. When the same blood samples were measured twice, six widely used epigenetic clocks disagreed with themselves by up to nine years between the two runs, larger than any effect reported on this page. Versions of the same clocks rebuilt from principal components brought most repeat measurements within one and a half years of each other (Higgins-Chen, Nature Aging, 2022; PMID 36277076).
So an individual reading that falls, or rises, after a protocol can reflect the measurement rather than the person. The trials above found their effects across groups. They did not establish what any one person's pair of readings means.
The interventions
Tier 2 / Multi-domain
Multi-domain methylation-supportive program
The strongest clock signal in this section. Eight weeks of a structured program combining a methyl-donor-rich diet, sleep, exercise, and targeted supplements, tested in a small controlled human trial.
Tier 2 / Alternative
Fasting-mimicking diet
Three monthly five-day cycles of a calorie-restricted, plant-based, micronutrient-complete program. The clock figure comes from a secondary, exploratory analysis of a 2024 RCT, which is why the effect is shown with that caveat.
Tier 3 / Specific population
Vitamin D3 repletion
Not a general recommendation. The clock effect was seen specifically in overweight or obese people with suboptimal vitamin D who had not supplemented before. Outside that group the expected effect is smaller or absent.
Tier 4 / Long-term pattern
Mediterranean diet pattern
The smallest clock effect here and the longest commitment, but the deepest general-health evidence base of any intervention on this platform. The clock figure is from a subgroup; the full cohort did not reach significance. This is the one Health A on the list.
Dietary pattern
Whole-food plant-based diet
Strong and consistent biomarker evidence from randomized trials, which earns the Health B. No randomized trial with hard endpoints has isolated this diet on its own, and no single clock RCT anchors a specific year figure, so the clock evidence is held at limited.
Foundational practice
Structured exercise
The deepest hard-endpoint longevity evidence of anything on this list, which is why the Health grade is high. The epigenetic-clock evidence specific to exercise is still preliminary and comes from small uncontrolled studies, so no defensible clock-year figure is claimed and the Clock grade is held at C.
* Clock effect shown with its caveat: the figure comes from a subgroup, a secondary analysis, or a specific population rather than a powered primary endpoint The one outcome a trial names in advance as its main test. Results on other outcomes carry less weight.. See each protocol page for the exact study and its limitations.
How these interventions are chosen
An intervention appears here only if it has been measured against a biological-age clock in human participants. Mechanism, animal data, and popularity do not qualify an intervention for this list. Where the human clock evidence is weak, the Clock grade says so, and the honest reason to adopt the intervention is usually the Health grade, not the clock.
Biological-age clocks are surrogate markers. A lower clock reading is encouraging, but it is not a measured increase in your lifespan. Treat the clock as a feedback signal layered on top of interventions you would have good reason to do regardless.