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The PhenoAge clock, as its name suggests, was trained against the phenotypes (effects) of aging, and the GrimAge clock was specifically trained against plasma proteins and the effects of smoking.Ī total of 490 people were tested as part of the epigenetic study, and they were tested for eight metrics: walking speed, grip strength, polypharmacy, the Fried Frailty Score, the Mini-Mental State Exam, the Montreal Cognitive Assessment, the Sustained Attention Reaction Time Task, and the Choice Reaction Time Task.Īll four clocks were studied with this cohort, and the cohort was investigated for social mobility, which is a strong predictor of health outcomes, as well as other factors known to affect health, such as body mass index (BMI), smoking history, and alcohol consumption while such things may affect epigenetics as well, it is of marginal value to have a clock that turns out to only successfully measure their influence. This is where the second-generation clocks shine.

Most importantly, they are not significantly correlated with all-cause mortality, making them practically useless for estimating the efficacy of a therapy that is designed to extend lifespan and healthspan. This study has found that with these clocks, increases of epigenetic age over calendar age do not correlate with physical ability tests, cognitive tests, or the need for a patient to be prescribed multiple drugs (polypharmacy). Unfortunately, these two first-generation clocks are ill-suited for measuring the physical effects of age acceleration. If such a clock is truly measuring the effects of aging, if a person is epigenetically older than the clock signifies, that person should be at greater risk for age-related diseases than a person who has not experienced such age acceleration. Ideally, it would be possible to use this kind of analysis to measure age acceleration effects. Horvath (who contributed to this paper) and Hannum are very good at guessing calendar age: it is possible to take a cell sample, analyze it using one of these clocks, and accurately guess how old the donor is.

Did previous clocks use the wrong target?Īs the researchers explain, the first-generation epigenetic clocks of Drs.