Healthspan.

Epigenetic age tests: what your result can and can't tell you

Evidence grade: Moderate. Large human studies link some clocks to mortality and disease. But that is association, measurement noise can be large, and evidence that changing your score changes your health is limited. See how we grade.

What an epigenetic age test measures

These tests read DNA methylation, chemical tags on DNA that shift with age. An algorithm, called a clock, turns the pattern into an age estimate.

The first widely used clocks appeared in 2013. Steve Horvath built a multi-tissue clock from about 8,000 samples covering 51 healthy tissues and cell types. It uses 353 sites on the genome [1]. Hannum and colleagues built a blood-based model from more than 450,000 methylation markers in 656 people aged 19 to 101 [2]. These first clocks were trained to predict calendar age. Horvath's clock read close to zero for embryonic stem cells, and cancer tissue showed marked age acceleration [1]. That suggested the clock was picking up something biological, not just counting years.

Newer clocks aim at health, not birthdays

Later clocks were trained on health outcomes instead.

  • PhenoAge was built using clinical measures. It predicted all-cause mortality, cancers, healthspan, physical functioning and Alzheimer's disease better than earlier measures [3].
  • GrimAge combines methylation-based estimates of seven blood proteins and smoking pack-years. In validation data from thousands of people it predicted time to death, coronary heart disease and cancer [4].
  • DunedinPACE estimates the pace of aging rather than an age. It was built from a birth cohort tracked across two decades on 19 markers of organ-system health. It showed high test-retest reliability and was linked to morbidity, disability and mortality [5].

GrimAge stood out among the clocks of its time for predicting time to death [4]. DunedinPACE showed effect sizes similar to GrimAge and added some prediction beyond it [5]. All of this comes from large population studies. A clock that predicts risk across thousands of people is less precise for one person.

So when a test reports your "biological age", ask which clock it uses. Different clocks answer different questions.

How reliable is one result?

Less than the neat number suggests. A 2022 study in Nature Aging found that technical noise alone produced deviations of up to 9 years between repeat measurements of the same sample for six prominent clocks. Retrained versions of those clocks brought most repeats within 1.5 years [6].

What that means for you: a single result is a rough estimate. A change of a few years between two tests may be noise, not biology. Ask the provider which clock they use and what its repeat-test error is.

Can you change your epigenetic age?

Possibly, a little, but evidence is early. In the CALERIE trial, 220 adults without obesity were randomized to a 25% calorie-restriction target or their usual diet for two years. A later analysis found the intervention slowed DunedinPACE, but did not significantly change PhenoAge or GrimAge, and the effects were small [7]. That was a post hoc analysis, and it did not show the change led to better health.

Be careful with products that promise to "reverse" your epigenetic age. A lower score is not the same as a longer or healthier life until trials show it.

How to use a result sensibly

  • Treat it as one data point, not a diagnosis.
  • Do not start, stop or change any medication because of it. Talk to a doctor about anything that worries you.
  • If you retest, use the same provider and clock, and expect some noise.
  • Keep tracking the standard markers your doctor already checks, like blood pressure and blood lipids. Our guide to the biological age blood test covers a related approach.
  • Spend most of your effort on what is already known to matter: the habits in our foundations protocol.

Frequently asked questions

What is an epigenetic age test?

It is a test that reads DNA methylation patterns and uses an algorithm called a clock to estimate a biological age or a pace of aging.

Are epigenetic age tests accurate?

Some clocks predict mortality and disease in large studies, but individual results can be noisy. One study found technical noise alone caused differences of up to 9 years between repeat measurements for several common clocks.

What is the difference between GrimAge, PhenoAge and DunedinPACE?

PhenoAge was built from clinical measures of health. GrimAge combines methylation estimates of blood proteins and smoking history. DunedinPACE estimates how fast you are aging now rather than an age in years.

Can I lower my epigenetic age?

Evidence is early. In one randomized trial, two years of calorie restriction slightly slowed DunedinPACE but did not significantly change PhenoAge or GrimAge. No trial has shown that lowering a score improves health.

Should I change my treatment based on an epigenetic age test?

No. These tests are not diagnostic. Talk to a doctor before changing any medication or treatment.

Sources

  1. DNA methylation age of human tissues and cell types. Genome Biology, 2013. https://pubmed.ncbi.nlm.nih.gov/24138928/
  2. Genome-wide methylation profiles reveal quantitative views of human aging rates. Molecular Cell, 2013. https://pubmed.ncbi.nlm.nih.gov/23177740/
  3. An epigenetic biomarker of aging for lifespan and healthspan. Aging (Albany NY), 2018. https://pubmed.ncbi.nlm.nih.gov/29676998/
  4. DNA methylation GrimAge strongly predicts lifespan and healthspan. Aging (Albany NY), 2019. https://pubmed.ncbi.nlm.nih.gov/30669119/
  5. DunedinPACE, a DNA methylation biomarker of the pace of aging. eLife, 2022. https://pubmed.ncbi.nlm.nih.gov/35029144/
  6. A computational solution for bolstering reliability of epigenetic clocks: Implications for clinical trials and longitudinal tracking. Nature Aging, 2022. https://pubmed.ncbi.nlm.nih.gov/36277076/
  7. Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial. Nature Aging, 2023. https://pubmed.ncbi.nlm.nih.gov/37118425/