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Epigenetic clock changes correspond inconsistently to clinical changes in ageing studies

In human geroscience intervention studies, epigenetic-clock changes matched clinical-outcome changes inconsistently, and no study validated a clock as a surrogate.

This systematic review asked whether intervention-induced changes in DNA-methylation clocks match clinical outcome changes in human geroscience studies. Twenty-six studies were included: 13 comparative and 13 single-arm pre-post designs. Fifteen were mixed, six indeterminate and four jointly inconclusive; one uncontrolled study was uniformly concordant for intermediate outcomes. No comparative study or study of patient-important outcomes was uniformly concordant, and none validated a clock as a surrogate endpoint. Eleven studies assessed individual-level associations, responder differences or mediation, but clear findings were isolated and not replicated. No combination of intervention, clock and outcome allowed meta-analysis, and certainty of evidence was very low throughout.

Why it is interesting: The review tests whether epigenetic clocks can stand in for clinical outcomes in ageing intervention studies. Favourable signals were mainly in selected intermediate outcomes, and clocks remain exploratory rather than validated surrogates.

Source
Experimental Gerontology, 24 October 2026
Paper
Concordance between changes in epigenetic clocks and changes in clinical outcomes in geroscience intervention trials: A systematic review
Authors
Yi M, Li M, Li H, Gui Y, Wang Z
DOI
10.1016/j.exger.2026.113367
Type
Peer-reviewed article
Design
Systematic review of 26 human geroscience intervention studies (13 comparative, 13 single-arm pre-post) reporting paired DNA-methylation clock and clinical outcome change, with risk-of-bias and GRADE certainty assessment
Verdict
Refines prior evidence
Driver
Slowing ageing itself
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