The distribution of adipose tissue is influenced by gender and by age, shifting from
subcutaneous to visceral depots with longevity, increasing the development of several
aging-related diseases and manifestations such as obesity, metabolic syndrome, and
insulin resistance. Epigenetics might have an important role in aging processes.
The aim of this research was to investigate the interactions between aging and
epigenetic processes and the role of visceral adipose tissue, insulin resistance, and
dyslipidaemia. Two different study samples of 366 and 269 adult participants were
analyzed. Anthropometric, biochemical (including the triglycerides-glucose (TyG) index),
and blood pressure measurements were assessed following standardized methods.
Body composition measurements by Dual-energy X-ray absorptiometry (DXA) were
also performed for the second sample. Methylation data were assessed by Infinium
Human Methylation BeadChip (Illumina) in peripheral white blood cells. Epigenetic age
acceleration was calculated using the methods DNAmAge (AgeAcc) and GrimAge
(AgeAccGrim). Age acceleration (AgeAccGrim) showed better correlations than AgeAcc
with most of the measured variables (waist circumference, glucose, HOMA-IR,
HDL-cholesterol, triglycerides, and TyG index) for the first sample. In the second sample,
all the previous correlations were confirmed, except for HOMA-IR. In addition, many of
the anthropometrical measurements assessed by DXA and C-reactive protein (CRP) were
also statistically associated with AgeAccGrim. Associations separated by sex showed
statistically significant correlations between AgeAccGrim and HDL-cholesterol or CRP in
women, whereas, in men, the association was with visceral adipose tissue mass DXA,
triglycerides and TyG index. Linear regression models (model 1 included visceral adipose
tissue mass DXA and TyG index and model 2 included HDL-cholesterol and CRP) showed
a significant association for men concerning visceral adipose tissue mass DXA and TyG
index, while HDL-cholesterol and CRP were associated in women. Moreover, structural
equation modeling showed that the TyG index was mediating the majority of the visceral adipose tissue mass action on age acceleration. Collectively, these findings showed that
there are different mechanisms affecting epigenetic age acceleration depending on sex.
The identified relationships between epigenetic age acceleration and disease markers
will contribute to the understanding of the development of age-related diseases