Epigenetic clocks of various sorts have become quite diverse in recent years, and it is worth noting that more recent clocks do not exhibit the insensitivity to physical fitness that was a characteristic of the earliest clocks. We should assume that any clock will have quirks, even those that do well with exercise. Since the relationships between specific causes and dysfunctions in aging and the specific epigenetic marks used in epigenetic clocks remain almost entirely unknown, a clock cannot be trusted to correctly assess the impact of any specific intervention on aging. The clock has to be calibrated against that intervention. This defeats the whole point of the exercise, which is to find ways to quickly assess the merits of potential novel rejuvenation therapies, without having to run lengthy studies to assess life span and mortality.
Epigenetic clocks include several specific measures such as HorvathAge, HannumAge, SkinBloodAge, LinAge, WeidnerAge, VidalBraloAge, ZhangAge, and PhenoAge. Ageing research increasingly focuses on understanding the biological mechanisms that contribute to ageing and how lifestyle factors, such as physical activity (PA), can influence these processes. The above epigenetic ageing indicators represent different approaches to estimating biological age and have been associated with various health outcomes. Recent studies have highlighted the stronger and more consistent associations between PA and epigenetic aging, especially with GrimAge.
This study investigates the relationship between physical activity (PA) levels and DNA methylation (DNAm)-predicted epigenetic clocks in a U.S. population sample (n = 948, mean age 62, 49% female). The eight above mentioned epigenetic clocks were analyzed, revealing that higher PA levels were significantly associated with younger biological ages across all indicators, with the strongest effects observed for SkinBloodAge and LinAge. Subgroup analyses indicated that these associations were more pronounced among non-Hispanic whites, individuals with a BMI of 25-30, and former smokers, suggesting that the impact of PA varies across different groups. These findings emphasize the role of PA in slowing biological ageing and reducing age-related health risks.
Link: https://doi.org/10.1038/s41514-025-00217-0
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