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Is the change detected by the clock purely a function of time and completely age-related? Or, do they provide a measure of the intrinsic speed of biological aging, which can be related to health, fitness and life expectancy? DNA methylation (dnam) is formed by genetic and environmental factors and is regulated by aging

The “epigenetic clock” based on DNA methylation (dnam) has become a widely used biomarker of aging, and its accuracy and practicality exceed the determination of telomere length

It is commonly known as dnam age (dnamage), which is a CPG based biological age estimator suitable for humans and mice

All these clocks have a common feature — they rely on the methylation status of a preselected subset of CPGs, which are assigned their own weights and collectively used to estimate age

A key question is: are the changes detected by these dnamage clocks purely a function of time and completely age-related? Or, do they provide a measure of the intrinsic speed of biological aging, which can be related to health, fitness and life expectancy? Evidence from human epidemiological studies shows that some dnamage clock detection methods perform well in predicting life expectancy. Compared with chronological age, younger dnamage means that the speed of biological aging slows down, and is associated with reduced disease risk and longer life span

Recently, researchers published a study on agingCell, reporting the relationship among epigenetic aging, body weight (BW) and life span

Researchers found that mice from 12 homologous strains of the BXD family showed more than 2-fold difference in life span

The researchers detected genome-wide DNA methylation levels in 70 liver samples, mainly from female mice aged 6-25 months, which were maintained on normal diet or high-fat diet (HFD)

Based on DNA methylation data, researchers defined a subset of CpG regions associated with age, body weight at young age, and diet related lifespan

Researchers found that these age-related differentially methylated CpG regions (age DMRs) have obvious genomic features, and DNA methylation increases over time at sites with high CpG density and low average methylation, such as promoters and exons

Weight related CpG regions are enriched in introns, tend to have lower methylation in higher weight mice, and are inversely proportional to gene expression (i.e., higher mRNA levels in higher weight mice)

Influence of body weight and high-fat diet on longevity the longevity related CpG region is related to genes involved in longevity regulation, including the telomerase reverse transcriptase gene TERT, which has both low methylation and high expression in the longevity strain

The epigenetic clock defined by age DMRs showed that mice with shorter lifespan lines were characterized by accelerated aging

Both higher body weight and high-fat diet are associated with accelerated epigenetic aging

Therefore, this result highlights the age accelerating effect of greater body weight

In addition, the researchers demonstrated that the measurement of epigenetic aging derived from age DMRs can predict the difference in lifespan between female BXD members caused by genotype and diet

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