23 December 2020

Is it about DNA methylation?

Why do women live longer than men?


How deep are the differences between men and women? – a question that has been tormenting the minds of scientists, poets, and philosophers for thousands of years. Why do we react so differently to stress, to changes in environmental conditions, perceive information differently and, of course, why do women on average live longer than men?

Regardless of race, place of residence, average life expectancy in the region, level of medical care, maternal mortality and other factors, women always and everywhere live longer than men on average. Somewhere this difference is 2-3 years, for example in Europe, and in some regions of Russia it reaches 8 years and even 12 years. Life expectancy may increase significantly, as in Japan, as a result of the development of medical technologies and an increase in the quality of life, but a statistically significant difference between men and women still persists.  What is the reason?

Scientists emphasize that the risk of age-related diseases directly depends on the age of a person, but not so much on the "chronological" (the one indicated in the passport) as from the "biological" (the one that really reflects the processes of accelerated or delayed aging). However, how to find out the biological age is still an open question. One of the most promising methods is the "epigenetic clock". It turns out that the work of genes is regulated by chemical modifications of DNA. The gene may be "blocked" as a result of methylation of certain DNA sites, and on the contrary, become active if these "tags" are removed.

Amazingly, the level of methylation of some genes increases or decreases with age evenly, forcing us to recall the myth of ancient Greek moirs inexorably weaving the threads of fate. By measuring the level of methylation of certain DNA points, you can thus "spy" the internal age of the cells of the body, find out how much their "epigenetic clock" shows.

Is it possible that the "epigenetic clock" in men and women goes differently? A study recently published in the journal Aging analyzed age-dependent changes in DNA methylation in men and women.

"To conduct such a study, we need absolutely non–trivial solutions for processing large-dimensional data, because each methylome (analysis of human DNA methylation sites) includes about 450 thousand points," said Mikhail Ivanchenko, head of the study, Doctor of Physical and Mathematical Sciences, Vice-Rector for Scientific Work at UNN.

Such a problem cannot be solved without the use of complex mathematical methods of analysis. Scientists of Nizhny Novgorod State University have shown that there are DNA sites (CpG sites) with different trajectories of age-related changes in methylation in men and women. Analysis of such sites and the functional activity of the genes to which they belong indicates that these are not only loci associated with hormonal regulation, but also genes with general biological functions.

Thus, among the large number of genes that change methylation with age, there is a small but significant group in which age-related changes occur in men and women differently. For example, these are the genes FIGN (encodes a protein that participates in cell division) and PRR4 (encodes a protein with antimicrobial properties).

Further analysis showed that the spread of the methylation level increases with age, and the increase in the variability of methylation in men is 15 times higher than in women.

"Is this crucial for a person's life expectancy? What processes and at what age are the triggers for the development of such pronounced differences in the level of methylation in older people? Is it possible to predict the development of age-dependent pathologies decades before their first manifestation? Is it possible to prevent the development of the disease? "all these questions have yet to be answered," said Claudio Franceschi, Europe's leading gerontologist, head of the UNN megagrant.

However, the significance of the results already obtained cannot be overestimated. This is not only a pioneering study of gender-specific DNA regulation in the context of aging, but also a fundamentally new approach that reveals previously unknown molecular mechanisms of gender differences in life expectancy, the study of which in the future will help prevent the development of age-related diseases.

Article by Yusipov et al. Age-related DNA methylation changes are sex-specific: a comprehensive assessment published in the journal Aging.

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