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

Abstract

BackgroundHuman 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.MethodsTo 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.ResultsThe 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.ConclusionTaken 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-016-0301-7) contains supplementary material, which is available to authorized users.

Associations between environmental breast cancer risk factors and DNA methylation-based risk-predicting measures

“…Similar to previous studies [23,19,[24][25][26], we also found epigenetic age acceleration being positively associated with lifestyle risk factors including BMI, smoking and alcohol drinking. These results suggest that an unhealthy lifestyle could accelerate biological ageing, consistent with both epigenetic age acceleration and an unhealthy lifestyle potentially being associated with an increased breast cancer risk.…”

“…The variance of epigenetic age acceleration has also been suggested to be influenced by environmental factors [22]. Lifestyle factors, such as smoking, alcohol drinking, obesity, exercise and diet [23,19,[24][25][26], and hormone-related breast cancer risk factors, such as age at menarche and age at menopause [27,28], have been found to be associated with epigenetic age acceleration.…”

Accelerated Epigenetic Ageing in Major Depressive Disorder

“…It was previously unknown however, whether accelerated ageing effects at the level of methylation using such predictors would be seen in MDD, and how these may be mediated by other factors, for example BMI. There are known robust reciprocal links between obesity and depression (26), and the role of increased BMI and shortened lifespan has also been extensively studied (35).…”

“…These included self-reported smoking and alcohol intake/consumption (as described above). In addition, since there is a known relationship between obesity and accelerated epigenetic ageing (26), and between obesity and MDD (27), we also explored the contribution of body mass index (BMI, as a proxy for obesity) to the relationship between EAA and depression status.…”

Obesity and ageing: Two sides of the same coin

“…Notably, BMI is associated with epigenetic ageing in various tissues, except in young adults. One of the possible explanations is that obesity‐accelerated epigenetic ageing takes place over a relatively long period of time and young adults have not been exposed to obesity long enough for noticeable alterations in epigenetic ageing to occur . To support the association between BMI and epigenetic ageing, a longitudinal study has suggested that an increase in BMI is associated with an increase in epigenetic age acceleration, although the correlations in liver are much more significant than those in blood.…”