August 5, 2021

Sex change in mice to understand why women live longer | Science

Sex change in mice to understand why women live longer | Science



Throughout the world, women live longer than men, regardless of their culture or socioeconomic status. In extreme cases, as in Russia, the difference reaches 12 years; in Spain it stays at something less than six. Behind these differences is the greater recklessness of males from a certain age. During the first years of life, the causes of death of boys and girls are similar diseases, but after 10 years, traffic accidents, drownings and later violent confrontations cause children to die more. However, even when one takes into account the higher consumption of alcohol and tobacco or the greater tendency to put men at risk, women are more long-lived.

This difference between sexes, shared by most animals, is still a mystery. As explained Manuel Collado, head of the laboratory of Aging, Cancer and Stem Cells at the Health Research Institute of Santiago de Compostela (Idis), "it was assumed that the disparity was due to hormones and the gonads [testículos y ovarios] and its different effects on the organism. " According to this hypothesis, male sex hormones would damage the immune system and increase the risk of cardiovascular problems, and studies with animals indicate that castrating males prolongs their life. In humans, this effect was observed in individuals institutionalized in American psychiatric institutions who were castrated. Those who underwent this surgery lived an average of 14 more years and it was observed that the sooner the testicles were removed, the greater the effect on life expectancy. In another study with historical records on the lives of eunuchs of the Joseon dynasty in Korea, similar results were found.

Extruding the testicles can prolong life, both in humans and animals

In this quest to find the source of female longevity or the masculine feature that shortens life, a team of scientists from the University of California in San Francisco has devised an ingenious experiment that it has just been published in the magazine Aging Cell. They used mice genetically identical to those that divided into four groups. On the one hand, conventional males and females in which they had two X chromosomes and ovaries and they an XY pair and testicles, and on the other, hybrids with the pair of X chromosomes and testicles or the pair XY and ovaries. The mice with two X chromosomes and ovaries were the longest lived, but that same combination also prevented premature death to those who had testicles.

The lead author of the paper, UCSF researcher Dena Dubal, acknowledges that they still do not understand how the second X chromosome reduces mortality during aging, but its results add to many others that point to a protective effect of a second chromosome X. The Y chromosome contains a few dozen genes, such as those that cause the testicles to grow or grow the beard, but nothing apparently fundamental. The X has hundreds and all human beings need at least one to live. Having two copies of a tool essential for survival can protect against the dangers of existence, including having a pernicious mutation on the X chromosome. In the case of females, the expression of the damaged gene would be silenced and the copy of the second chromosome would compensate for the defect. Meanwhile, the males would suffer the effects of the error by not having a backup copy. However, the authors do not rule out the opposite and it is some activity of the Y chromosome that is harmful.

Dubal argues that the greater relevance of the mother figure in the survival of the offspring can also favor a boost to their longevity. "When you live longer, you can ensure the welfare of your offspring and perhaps even the offspring of your offspring," he says. Studies like yours can begin to unravel the mechanisms that explain the difference.

Some revisions, like one published by researchers from the University of Alabama in the journal Cell Metabolism in 2016, they point to the antioxidant and anti-inflammatory properties of estrogen, a female hormone. Both inflammation and oxidative damage have been linked to aging in old age and the ability of estrogens to reduce bad cholesterol, a substance that increases the risk of cardiovascular problems, has also been observed.

Along with these benefits, the longevity of women has a negative counterpart. Although they live longer, they seem to have worse health than men. Data from advanced countries indicate that they go to the doctor more, take more medications, lose more days of work for health reasons and spend more hospital days. One possibility that could explain this data is that women pay more attention to their health and are less reluctant to go to the doctor, but some objective measures of well-being have also obtained worse results for them in countries all over the world and even in societies. indigenous as the Bolivian Tsimane. Studies on aging processes, which want to understand the basis of the differences in longevity between the sexes in order to apply the advantages to all, will also try to face this paradox.

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