Epigenetic clocks

Age estimates built from DNA methylation patterns at specific sites in the genome, accurate across populations and still unreliable for tracking one person over months.

How they work

Chemical methyl tags on DNA change in predictable ways with age. By measuring methylation at a few hundred selected sites and weighting them, an algorithm can estimate chronological age remarkably closely. Horvath's 2013 clock did this across many tissues at once.

Later clocks were trained differently. Rather than predicting calendar age, they were trained to predict mortality or health outcomes, which made them more informative about risk and less impressive at guessing your birthday.

Pace of aging is a different measurement

DunedinPACE, developed in the Dunedin birth cohort, does not estimate age. It estimates rate of biological change per calendar year, derived from repeated measures of organ system function in the same people over decades.

That distinction matters for anyone considering a repeat test. A pace measure is designed to move; an age estimate mostly is not.

The reliability problem

Technical noise in methylation arrays is substantial. Analyses of test to retest reliability found that several widely sold clocks vary by multiple years between duplicate samples from the same blood draw, which is larger than the change most interventions would produce.

So a two year improvement on a consumer report after three months of effort may be measurement noise rather than progress. The practical guidance is to leave long intervals between tests and to read a single result as one data point. As a research tool, and averaged across many people, the clocks are genuinely valuable.

Baseline does not sell epigenetic age testing. We would rather track markers that are reliable enough to act on, which is what the phenotypic age calculator uses.

References

  1. Horvath S. DNA methylation age of human tissues and cell types. Genome Biol. 2013.
  2. Belsky DW, et al. DunedinPACE, a DNA methylation biomarker of the pace of aging. eLife. 2022.
  3. Higgins-Chen AT, et al. A computational solution for bolstering reliability of epigenetic clocks. Nat Aging. 2022.