Epigenetic Aging Clocks Compared: Which One Predicts Mortality Best?

Highlights

• The GrimAge epigenetic clock outperformed other aging clocks—PhenoAge, Horvath 1, Hannum, and DunedinPACE—in predicting mortality.
• All aging clocks assessed outperformed measurements of the lengths of telomeres—protective DNA caps at the ends of chromosomes—in predicting mortality.

As published in Aging Cell, Zonderman and colleagues from the National Institute on Aging unveil data suggesting that the epigenetic aging clock GrimAge outperforms other clocks in predicting mortality. Furthermore, all of the aging clocks assessed, PhenoAge, Horvath 1, Hannum, and DunedinPACE, in addition to GrimAge, fared better than telomere length in predicting mortality. These findings support the notion that epigenetic aging clocks—which estimate how old your body is functionally rather than how many years you have lived based on DNA molecular tagging patterns—work better than telomere length (another way to assess age based on physiological function). Moreover, the study suggests that the GrimAge epigenetic aging clock may work better than other ways of assessing epigenetic age.

The study correlated mortality data from three groups of participants (corroborated with data from the National Death Index) with biological age measurements as assessed with aging clocks. In doing so, the researchers found that these biological aging clocks that analyze chemical tags on DNA that regulate gene activity (epigenetic clocks), particularly GrimAge, outperformed another way to assess age based on physiological function—telomere length. This data could be crucial for lending credulity to measuring biological age with epigenetic clocks.

Even more, the study provided a comparison of different epigenetic clocks. In that regard, Zonderman and colleagues found that GrimAge outperformed other epigenetic clocks in predicting mortality, according to the study’s statistical analyses.

Interestingly, researchers who developed the GrimAge epigenetic aging clock, including UCLA’s Steve Horvath, developed this particular aging clock to predict mortality and healthspan—the duration of life without one or more debilitating diseases. This sets GrimAge apart from other epigenetic aging clocks, such as DunedinPACE, which was trained to correlate DNA tagging pattern changes with physiological decline over time. In that sense, if other researchers can replicate this study’s findings, possibly with different statistical analysis methods, it could be the case that GrimAge works better to assess what could matter most—how long you will live.

GrimAge Outperformed Other Aging Clocks to Predict Mortality

Because associations between epigenetic age and telomere length with mortality have remained understudied, the National Institute on Aging researchers sought to find which methods work best to predict mortality. To this end, Zonderman and colleagues utilized data from three groups of aged US individuals, including between 3,000 and 4,000 participants, and matched their death records from the National Death Index. They ran large-scale statistical analyses of mortality from these three groups of participants and compared them to mortality predictions from the five epigenetic age clocks and from telomere length assessments.

Interestingly, all of the epigenetic aging clocks outperformed telomere length in predicting mortality. Furthermore, among the epigenetic clocks, GrimAge outperformed the rest. These findings suggest that epigenetic aging clocks that assess biological age work better than other ways to measure biological age, such as telomere length, and that GrimAge works best among the epigenetic clocks.

According to Zonderman and colleagues, epigenetic clocks measure different aspects of aging, namely, DNA molecular tagging patterns, compared to telomere length, the shortening of which has been linked to cellular senescence and cellular oxidative stress (where high levels of damaging reactive molecules accumulate). This means that the study’s findings lend support to the notion that changes to DNA molecular tagging patterns may better predict how fast someone ages compared to other biological age assessments, like telomere length.

Whether You Should Get Your Epigenetic Age Measured

Following what this study from Zonderman and colleagues suggests, anyone interested in uncovering how long he or she may live could turn to using the GrimAge assessment of epigenetic age. Along those lines, taking this test involves taking a small blood sample at home and mailing it to a laboratory, a process that takes only about five minutes, according to My Aging Tests. Moreover, the test comes with a price tag of around $325.

Once someone has taken this kind of biological age assessment, consulting with a physician, preferably one familiar with longevity science, could help to slow biological age, especially if the results suggest accelerated aging. In that regard, some possible ways to slow biological age include adhering to a regular exercise schedule, maintaining a balanced diet, prioritizing sleep, managing stress levels, and avoiding smoking and excessive alcohol consumption. Taking steps to find how fast you are aging could stimulate anyone to optimize lifestyle choices, adopting habits like those mentioned, in an effort to maximize healthspan and lifespan.