A pooled analysis combined data from 51 intervention studies and applied a standardized panel of 16 epigenetic clocks plus 94 additional DNA methylation biomarkers measured in blood. These epigenetic markers estimate biological age — a physiological measure distinct from chronological age — by assessing DNA methylation patterns that change across the lifespan.
Using the harmonized dataset, investigators evaluated how a range of interventions affected these methylation-based biomarkers. Two broad lifestyle approaches showed consistent associations with reduced epigenetic aging: adherence to a healthy diet (examples reported include Mediterranean, low-carbohydrate, or low-fat diets) and regular physical exercise. Across the studies, these lifestyle interventions tended to produce consistent responses across different clocks.
Pharmacological interventions produced the largest average effects on the panel of biomarkers. The medications highlighted in the analysis that significantly decreased age across all 16 epigenetic clocks were metformin, semaglutide, and anti‑TNF therapies. The authors therefore report that some diabetes and weight‑management medications, and certain anti‑inflammatory biologics, were associated with measurable reductions in DNA methylation age measures.
By contrast, over‑the‑counter supplements showed limited and inconsistent evidence of anti‑aging effects on these methylation biomarkers. The study authors and quoted investigators note that while supplements can be important for treating specific deficiencies or medical needs, the current evidence does not support generalized anti‑aging claims for supplements in otherwise healthy people.
The investigators emphasize that epigenetic biomarkers can reveal biological changes over months or years, offering a faster signal than waiting for long‑term outcomes such as disease incidence or mortality. However, these biomarker changes are indicators of change rather than proof that an intervention slows the biological processes that lead to worse health or earlier death.
External commentary included in the report cautions that some observed medication effects may reflect improvement in the participants’ underlying conditions rather than a direct anti‑aging action. Several of the contributing studies enrolled people with specific diseases or metabolic disorders, so lowering biological age on methylation clocks could partly represent recovery of metabolic or inflammatory health.
The report quotes a longevity researcher noting the value of the study’s scale and its standardized approach: harmonizing multiple longitudinal interventions and applying the same biomarker panel allowed more systematic comparisons of how different biomarkers respond to different interventions. That expert also suggested that newer biomarkers trained to predict mortality risk or the pace of aging, such as DunedinPACE and PCGrimAge, may be more responsive to interventions than clocks primarily trained to predict chronological age.
Corresponding author Raghav Sehgal, PhD, reiterated that while the results are interesting, they do not establish that these treatments should be given to healthy people specifically to slow aging. Medication use for anti‑aging cannot be recommended from biomarker changes alone, especially when many findings derive from clinical populations.
The authors and external reviewers underline a key limitation: changes in epigenetic clocks are not proven surrogates for improved healthspan or longevity. The study’s central question was whether these methylation measures detect change in response to interventions. The subsequent, essential step is to determine which biomarker changes — if any — reliably predict meaningful clinical outcomes such as preserved physical and cognitive function, reduced disease incidence, or longer healthy life.
Experts quoted in the article advise viewing epigenetic clocks as promising research tools rather than definitive clinical endpoints. They caution against interpreting a biomarker response as equivalent to evidence that an intervention slows aging. Long‑term randomized trials or longitudinal outcome data will be needed to link short‑term biomarker shifts to patient‑relevant benefits.
The practical recommendations reported alongside the study remain conventional, supported by the authors and by external experts: avoid smoking; engage in regular aerobic and resistance exercise; eat a balanced, Mediterranean‑style diet; maintain a healthy weight; limit alcohol intake; get sufficient, consistent sleep; and manage established cardiometabolic risk factors such as high blood pressure, high cholesterol, and diabetes.
The article reiterates that there is not yet a single intervention proven to broadly slow aging in humans. Instead, well‑established preventive behaviors and appropriate clinical management of chronic conditions currently offer the strongest evidence for supporting healthspan. Clinicians and patients should discuss supplements or medications case‑by‑case, recognizing that the study’s biomarker findings do not equate to clinical proof that an intervention will extend healthy life.