The Y chromosome and aging

Unpacking of the Y chromosome brought the old age of male fruit flies closer

Polina Loseva, N+1

American scientists have put forward a new hypothesis that aims to explain why males live less than females – in this case, flies. They noticed that there are more "meaningless" repeats in the Y chromosome of fruit flies than in the X chromosome, and these DNA regions are more twisted in young animals. With age, epigenetic labels disappear, DNA unfolds and mobile elements hidden inside these repeats "come out". By creating a line of females with an extra Y chromosome and males without a Y chromosome, the researchers confirmed that it is she who shortens the life of flies. The work was published in the journal Nature Ecology & Evolution (Brown et al., The Y chromosome may contribute to sex-specific aging in Drosophila).

In many animal species, females on average live longer than males. What caused this inequality is still not completely clear. Some researchers believe that sex chromosomes are to blame for everything: those animals whose sex is determined by a combination of chromosomes have a heterogeneous sex (that is, with a different type of chromosomes) lives less. Other scientists believe that it's not genetic factors – at least in mammals – but the influence of the environment: one sex may be more at risk or have poorer health.

At the same time, it is known that one of the engines of aging at the cellular level is the unwinding of DNA in "meaningless" areas. In such areas of the genome, mobile elements are often found, which, after unwinding, "go free" and get the opportunity to move around the genome, embed themselves in random places and disrupt the work of individual genes. Emily Brown and her colleagues from the University of California at Berkeley have suggested that the difference in life expectancy may be due to the different structure of sex chromosomes, since in drosophila the Y chromosome carries more "meaningless" repeat sequences than the X chromosome.

To begin with, the researchers measured the amount of heterochromatin ("twisted" sections of DNA) in the cells of young fruit flies and found that, as previously thought, females have about 20 MB less of it than males. After calculating the life expectancy of both sexes, scientists have confirmed that females live about 10 days longer.

Then the researchers compared the amount of heterochromatin in flies at 8 days and 64 days of life (this is almost the peak of life expectancy in males). It turned out that in old age, males become derepressed ("untwisted") one and a half times more sites than females. At the same time, most of these sites are located on the Y chromosome. There were a lot of potentially mobile elements among them. In females, the expression of 6 mobile elements increased with age, and 14 decreased. In males, the expression of only 4 mobile elements decreased, and 32 increased.

To check how unpacking of sex chromosomes affects life expectancy, the authors of the work created two lines of flies with a non-classical set of chromosomes. In drosophila, sex is determined by the ratio of the number of X chromosomes to the number of somatic (non-sexual) chromosomes in the presence of the Y chromosome. Therefore, it is possible to obtain males with the XO genotype (without the Y chromosome) or XYY and XXY females.

As expected, the XYY males lived less than normal males – about 40 days instead of the required 60. The life of XXY females turned out to be slightly shorter than that of ordinary females. But the HO males turned out to be long-lived, having overtaken both other males and females, and having lived up to 80-90 days. Thus, the authors of the work confirmed that it is the Y chromosome that shortens the life of males, and getting rid of it, on the contrary, prolongs their days.

B – survival curves of flies with different genotypes, C – average life expectancy (on the left – control individuals). A drawing from an article by Brown et al.

Now gerontologists have another argument against the Y chromosome at their disposal. Previously, it was believed that it could shorten the life of males due to the fact that it carries fewer genes than the X chromosome, or act indirectly through hormones (which, for example, suppress the activity of immunity). Now it has also been accused of being able to serve as a haven for mobile elements and release them into the wild over time. Next, scientists will have to check how relevant this is for other animals. In humans, for example, the number of active mobile elements in cells also increases with age. However, as the authors of the article note, both humans and flies have a high level of intraspecific variation in the number of repeats, so it is not yet clear how important the contribution of sex chromosomes is compared to individual differences.

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