GrimAge — the epigenetic clock of mortality

A second-generation epigenetic clock — the best predictor of mortality and disease

A dark clock face with protein molecules and a DNA helix — the GrimAge clock

GrimAge is a second-generation epigenetic clock developed by Steve Horvath's group (Lu et al., 2019). Its name alludes to the Grim Reaper: of all known clocks, GrimAge is the most strongly associated with the risk of death.

Instead of simply predicting calendar age, GrimAge uses DNA methylation to estimate surrogates of seven plasma proteins and smoking history, and then converts them into a "mortality age" in years.

What GrimAge is made of

GrimAge is built in two steps. First, DNA methylation is used to estimate surrogates of seven plasma proteins (adrenomedullin, beta-2-microglobulin, cystatin C, GDF-15, leptin, PAI-1, TIMP-1) and smoking history in "pack-years." Then these estimates are combined into a single indicator — age in years.

What it predicts

Of all known epigenetic clocks, GrimAge is the most strongly associated with mortality, as well as with time to coronary heart disease and cancer. The difference between GrimAge and calendar age is called AgeAccelGrim (GrimAge acceleration): the greater it is, the higher the risk.

Limitations

GrimAge largely reflects smoking and inflammation. It is a research indicator, not a clinical diagnosis. There is as yet no evidence that deliberately lowering GrimAge extends life, although quitting smoking predictably improves the indicator.

Calculate using this marker

Calculators where GrimAge is used directly:

Biological Age Estimate A quick estimate from height, weight, and body measurements — no labs needed Open PhenoAge (Levine) Nine blood markers — the formula from Morgan Levine et al., 2018 Open

Frequently asked questions

Why is GrimAge better than the Horvath clock?

The Horvath clock was trained to predict calendar age, whereas GrimAge was trained on real outcomes (mortality, disease). That is why GrimAge predicts the risk of death markedly better.

Can GrimAge be lowered?

Quitting smoking and a healthy lifestyle are associated in studies with less GrimAge acceleration. But there is still not enough evidence that lowering the indicator itself extends life.

Sources

info

This content is educational and does not replace consultation with a physician. Reference ranges may vary depending on the laboratory and method — rely on the ranges stated on your own test report.

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