Obesity accelerates epigenetic aging in middle-aged but not in elderly individuals

Background: Human aging is associated with profound changes in one of the major epigenetic mechanisms, DNA methylation. Some of these changes occur in a clock-like fashion, i.e., correlating with the calendar age of an individual, thus providing a new aging biomarker. Some reports have identified factors associated with the acceleration of the epigenetic age. However, it is also important to analyze the temporal changes in the epigenetic age, i.e., the duration of the observed acceleration, and the effects of the possible therapeutic and lifestyle modifications. Methods: To address this issue, we determined the epigenetic age for a cohort of 183 healthy individuals using blood samples derived from two time points that were 25 years apart (between 15-24 and 40-49 years of age). Additionally, we also determined the epigenetic ages of 119 individuals in a cohort consisting of 90-year-old participants (nonagenarians). These were determined by using the Horvath algorithm based on the methylation level of 353 CpG sites. The data are indicated as the deviation of the epigenetic age from the calendar age (calendar age minus epigenetic age = delta age, Delta AGE). As obesity is often associated with accelerating aging and degenerative phenotypes, the correlation of the body mass index (BMI) with the Delta AGE was analyzed in the following three age groups: young adults, middle-aged, and nonagenarian. Results: The data showed that BMI is associated with decreased Delta AGE, i.e., increased epigenetic age, in middle-aged individuals. This effect is also seen during the 25-year period from early adulthood to middle age, in which an increase in the BMI is significantly associated with a decrease in the Delta AGE. We also analyzed the association between BMI and epigenetic age in young and elderly individuals, but these associations were not significant. Conclusion: Taken together, the main finding on this report suggests that association between increased BMI and accelerated epigenetic aging in the blood cells of middle-aged individuals can be observed, and this effect is also detectable if the BMI has increased in adulthood. The fact that the association between BMI and epigenetic age can only be observed in the middle-aged group does not exclude the possibility that this association could be present throughout the human lifespan; it might just be masked by confounding factors in young adults and nonagenarian individuals.