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

Abstract

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, ΔAGE). As obesity is often associated with accelerating aging and degenerative phenotypes, the correlation of the body mass index (BMI) with the ΔAGE was analyzed in the following three age groups: young adults, middle-aged, and nonagenarian.

Results: The data showed that BMI is associated with decreased ΔAGE, 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 ΔAGE. 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.

Fig. 1

a Association between ΔAGE (difference between chronological age and epigenetic age in years) and BMI in young adults of the Young Finns Study (mean age of 19.2 years). Association is non-significant (r = −0.110, p = 0.138). b Association between ΔAGE and BMI in middle-aged individuals of the Young Finns Study (mean age of 44.2 years, follow-up from Fig. 1a). Correlation is significant (r = −0.281, p = 0.0001)

Fig. 2

Association between ΔAGE and BMI in nonagenarian individuals of the Vitality 90+ Study (Age of 90 years). Correlation is non-significant (r = 0.115, p = 0.211). However, it is noteworthy that the trend of correlation is opposite to corresponding ones of the young adults and middle-aged (Fig. 1a, b). This could be an indication of obesity paradox where higher BMI is beneficial for the elderly individuals

Fig. 3

Association between ΔAGE and change in BMI in a 25-year follow-up in middle-aged individuals of the Young Finns Study. Correlation is significant (r = −0.193, p = 0.009), indicating that increase in BMI has had an accelerating effect on epigenetic aging