17 March 2021

Methylation and longevity

Epigenetic clock explained the longevity of bats

Anna Muravyeva, N+1

Epigenetic DNA tagging coincided with longevity in bats, according to a study published in the journal Nature Communication (DNA methylation predicts age and provides insight into exceptional longevity of bats). Biologists analyzed 26 species of bats and found that DNA methylation is able to predict the life expectancy of animals. Changes in methylation associated with longevity were also associated with genes of innate immunity and tumor formation, gender and genes of transcription factors. This suggests that a long life for mice is provided, among other things, by an enhanced immune response and the fight against cancer.

The activity of genes in a cell changes according to the stage of development or other age-related changes. To suppress currently unused genes, cells use epigenetic labeling – they hang small methyl groups on DNA and histone proteins. Tags prevent enzymes from "settling" on DNA, which reduces the activity of genes and other genetic elements.

On the basis of methylation, it is possible to determine the age of the cell and the organism – the epigenetic clock. For the first time, this method of measuring age was proposed by Steve Horvath in 2013. He compiled a list of DNA sites, by methylation of which it is possible to determine quite accurately the age of the person to whom the cells belong. Methylation is also used to determine life expectancy – such studies have already been conducted on humans, rodents and dogs.

Biologists from the University of Maryland, led by Gerald S. Wilkinson, studied methylation in bats. Scientists were interested in the lifespan of bats – it is four times longer than that of mammals of the same size. In 712 animals of 26 species with a known age, a wing biopsy was taken to make a methylation analysis. After that, DNA was isolated from the cells and data on methylation of about 40 thousand sites were obtained by sequencing.

Methylation did correspond to the age of mice, which was shown for humans and other animals. The accuracy of determining the age by methylation was 0.74 years (while bats are able to live up to 42 years). Biologists have also identified a link between methylation and life expectancy: it turned out to be associated with both an increase in methylation in some sites and a decrease in others. These results show that a more "successful" adjustment of the epigenetic clock is associated with an increase in life expectancy.

Biologists analyzed sites whose methylation turned out to be associated with life expectancy. It turned out that many of them are also related to gender (p<0.0001). For Pallas Molossus molossus, it was shown that genes whose methylation is associated with longevity are also associated with immunity and often mutate in tumor cells (p=0.002 and p=0.016). Methylation associated with life expectancy has also affected regulatory elements – sites that do not belong to genes, but affect their activity. 

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