Faster Epigenetic Aging Linked to Higher Death Risk Across 381,000 Adults, Meta-Analysis Finds

That is the finding of a systematic review and meta-analysis posted on medRxiv by Tay and colleagues. It is a preprint, which means it has not been peer reviewed. The work pools observational studies in people, so it shows associations, not causes. 125 articles with 380,705 participants met the inclusion criteria, and 53 of them were combined in the metaanalyses.

The tests are called DNA methylation clocks. They read chemical tags on DNA and turn the pattern into an estimated age. "Epigenetic age acceleration" is the gap between that estimated age and a person's actual age. A positive gap means the DNA looks older than the calendar says.

The team searched six databases for studies published from January 2011 to April 15, 2026. They screened 42,023 records. Across the included studies, 48 distinct clocks were evaluated. Higher DNA methylation ages were associated with higher risks of death from any cause, from cardiovascular disease and from cancer.

The clearest results were for a clock called GrimAge, in general populations. In 31 cohorts with 53,642 people, each one-year increase in GrimAge acceleration was associated with a hazard ratio of 1.09 for all-cause death (95% confidence interval 1.08 to 1.11). A hazard ratio compares the rate of death between groups. Here, it means about 9% higher risk per year of acceleration.

For cardiovascular death, the pooled figure was 1.10 per year (6 cohorts, 30,751 people). For cancer death, it was 1.06 per year (5 cohorts, 27,187 people). The authors summarise this as roughly 6% to 10% higher risk per year across the three outcomes.

Newer versions of the clock scored somewhat higher. Per standard deviation of acceleration, GrimAge2 had a pooled hazard ratio for all-cause death of 1.65 (1.53 to 1.77), against 1.46 (1.38 to 1.55) for GrimAge. PCGrimAge scored 1.56 (1.36 to 1.78) against 1.51 (1.32 to 1.74) for the version it was compared with. The authors describe these differences as numerical. The PCGrimAge intervals overlap heavily.

What does this mean for a single test result? The study reports group-level averages. A hazard ratio describes how risk differs between large groups of people. It does not say what will happen to one person. A higher-than-expected epigenetic age is best read as a risk signal that tracks with outcomes in populations, not as a diagnosis of disease.

There are other reasons for caution. The all-cause GrimAge result had high heterogeneity (I² of 84.1%), meaning the studies differed a good deal from one another.

The authors also note what is still unknown. They write that further work is warranted to evaluate whether these clocks respond to interventions, and whether they have clinical utility. Those questions matter most for anyone deciding what a biological-age number should change. Watch for peer review of this analysis, and for studies testing whether clock scores move in step with real health outcomes after an intervention.

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