The Epigenetic Clock Does Not Reflect Long-Term Physical Activity Differences in Twins
Epigenetic clocks are a weighted algorithmic combination of specific DNA methylation markers, those that exhibit characteristic changes with age. The various iterations of the clock have a strong association with chronological age, and appear to reflect biological age as well, in that people with more pronounced age-related disease and populations with higher mortality rates tend to have a higher epigenetic age than their healthier peers. Since the clock was reverse engineered by analysis of DNA methylation and age data, there remains the question of what exactly it is measuring. There is no comprehensive map to definitively link changes in epigenetic markers with the progression of the causes of aging.
Thus it is presently hard for researchers to make good use of the clock in speeding up the development of potential rejuvenation therapies; given a result, there will be uncertainty over what the result means. Numerous studies have been carried out on the epigenetic clock and specific medical conditions and therapies. Some of the results are troubling, such as the one here. If one can take twins who have a lifetime of very different exercise habits behind them, and find that they have roughly the same epigenetic age, that is a challenge. The epidemiological and animal data on exercise, even the modest levels of physical activity discussed here, strongly indicates that it has a robust, measurable effect on mortality rate and risk of age-related disease. If that doesn't show up in the epigenetic clock, we must come back once again to ask just what is it that the clock measures.
Advances in the fields of molecular biology have produced novel promising candidate biomarkers and their combinations that may be considered as biological aging clocks. So far, one of the most promising new aging clocks is DNA methylation (DNAm) age, also known as the "epigenetic clock". DNAm age is a multi-tissue age estimate based on DNA methylation at 353 specific age-related CpG sites. It is determined with a special algorithm, which is publicly available. The epigenetic clock appears to be associated with a wide spectrum of aging outcomes, most consistently mortality. Discrepancy between DNAm age and chronological age, i.e., higher "age acceleration" predicts all-cause mortality.
So far, it is also not clear whether the genetic component in variation of DNAm age changes over a life span. On the other hand, some environmental exposures and behaviors such as infections, diet, alcohol use, smoking, and work exposures predispose to age-related diseases and increase probability of death. Only part of individual variation to life expectancy can be accounted for using known and measured characteristics and exposure. An epigenetic clock could provide insights into the mechanisms behind why some individuals age faster than others and are more prone to age-related diseases and accelerated decline in physical function.
Physical activity is a potentially modifiable behavior that could slow down the rate of cellular and molecular damage accumulation and blunt the decline in physiological function with increasing age. The purpose of the study was to estimate the magnitude of genetic and environmental factors affecting variation in DNAm-based age acceleration in young and older monozygotic (MZ) and dizygotic (DZ) twins with a focus on leisure time physical activity.
The relative contribution of non-shared environmental factors was larger among older compared with younger twin pairs [47% versus 26%]. Correspondingly, genetic variation accounted for less of the variance in older compared with younger pairs [53% versus 74%]. We tested the hypothesis that leisure time physical activity is one of the non-shared environmental factors that affect epigenetic aging. A co-twin control analysis with older same-sex twin pairs (seven MZ and nine DZ pairs, mean age 60.4 years) who had persistent discordance in physical activity for 32 years according to reported/interviewed physical-activity data showed no differences among active and inactive co-twins, DNAm age being 60.7 vs. 61.8 years, respectively. Results from the younger cohort of twins supported findings that leisure time physical activity is not associated with DNAm age acceleration.