Better Diet and Exercise Choices Slow the Progression of Epigenetic Aging in Distinct Ways
Epigenetic clocks were developed by correlating observed changes in DNA methylation with age. Aging produces characteristic changes in cell behavior due to damage and dysfunction. While the nature of these changes is the same in every individual, the pace at which aging processes differs somewhat, the result of differing lifestyle choices and environmental exposures, such as particulate air pollution and persistent viral infection. When measured epigenetic age is greater than chronological age, this is referred to as epigenetic age acceleration, and this appears to be a useful measure of the degree to which an individual is aging more rapidly than the average. GrimAge is one of the better epigenetic clocks developed in recent years, judging from the data produced to support correlation between the measured epigenetic age acceleration and known risk factors for greater risk of age-related disease and mortality.
Here, researchers show that a sustained improvement in diet and exercise slows the rate at which the GrimAge epigenetic clock advances. It is most interesting to see the research community closing in, step by step, on a way to actually measure the effects of interventions on the aging process. Of note, however, GrimAge seems to have much the same issue in this study as was noted for first generation epigenetic clocks, in that it is insensitive to the metabolic changes brought about by exercise. There is clearly work yet to accomplish in the production of good, comprehensive biomarkers of aging!
Several biomarkers of healthy aging have been proposed in recent years, including the epigenetic clocks, based on DNA methylation (DNAm) measures, which are getting increasingly accurate in predicting the individual biological age. The recently developed "next-generation clock" DNAmGrimAge outperforms "first-generation clocks" in predicting longevity and the onset of many age-related pathological conditions and diseases. Additionally, the total number of stochastic epigenetic mutations (SEMs), also known as the epigenetic mutation load (EML), has been proposed as a complementary DNAm-based biomarker of healthy aging.
A fundamental biological property of epigenetic modifications, in particular DNAm, is the potential reversibility of the effect, raising questions about the possible slowdown of epigenetic aging by modifying one's lifestyle. Here, we investigated whether improved dietary habits and increased physical activity have favorable effects on aging biomarkers in healthy postmenopausal women. The study sample consists of 219 women from the "Diet, Physical Activity, and Mammography" (DAMA) study: a 24-month randomized factorial intervention trial with DNAm measured twice, at baseline and the end of the trial.
Women who participated in the dietary intervention had a significant slowing of the DNAmGrimAge clock, whereas increasing physical activity led to a significant reduction of SEMs in crucial cancer-related pathways. There was no significant slowing of DNAmGrim associated with the physical activity intervention nor reduced EML associated with the dietary intervention. Our study provides strong evidence of a causal association between lifestyle modification and slowing down of DNAm aging biomarkers. This randomized trial elucidates the causal relationship between lifestyle and healthy aging-related epigenetic mechanisms.