The insidious chromosome
Scientists have found out why men live less than women
RIA Novosti, Vladislav Strekopytov.
Men die on average several years earlier than women. Scientists suggest that the problem is the accelerated destruction of the "male" Y chromosome with age. This affects the heart muscle, and heart disease is the main cause of death among the stronger sex.
Official statistics
In 2019, the World Health Organization devoted a special report to the issue of life expectancy. The data is grouped by gender, age and income level. The document notes that from 2000 to 2016, the average life expectancy in the world increased from 66.5 to 72 years. For men, it was 70.57 years, for women — 75.06, that is, 4.49 years more.
Over 16 years of observations, this gap has hardly changed. In poor countries it is less, in rich countries it is more. The same picture is in different income strata of the population.
WHO experts explain this by the fact that in economically disadvantaged regions and social groups, due to difficult conditions, lack of quality medical services and the prevalence of infections, people often fall short of natural old age. Therefore, the life span of representatives of different sexes is leveled.
The ratio of men and women in different age groups. WHO / World Health Statistics 2019.
Not just people
In all countries and at all times, men have passed away before women. Traditionally, this has been associated with wars, a tendency to risky behavior, less concern for health and bad habits. When medical statistics appeared, it turned out that representatives of the stronger sex are more likely to die from such ailments as coronary heart disease, lung diseases, cirrhosis of the liver and stroke.
Biologists began to look for an explanation at the physiological level. And they found out that the difference in life expectancy between the sexes exists not only in humans, but also in other mammals. And in general, in all species with sexual dimorphism. Moreover, females do not always live longer than males. It also happens the other way around. It all depends on the set of sex-determining chromosomes. Chromosomes are structures that contain DNA strands. Their function is to store, implement and transmit hereditary information.
Last year, scientists at the University of New South Wales in Australia compared the set of chromosomes with the life expectancy of males and females of 229 animal species. Among them are primates and other mammals, birds, reptiles, fish, amphibians, spiders, cockroaches, grasshoppers, beetles and butterflies.
The authors found that individuals with an identical pair of chromosomes, or homogamous, on average live longer. For example, male birds: they have two identical Z chromosomes and have a life expectancy seven percent longer than females who have two different chromosomes - Z and W.
In mammals, on the contrary, male cells contain two different sex chromosomes — X and Y. And the females have two identical X's, and they live on average 21 percent longer.
Illustration by RIA Novosti
Reserve player
To explain this inequality, scientists have proposed the hypothesis of an "unprotected X chromosome", according to which a homogamous sex, in case of damage to one of the chromosomes, its function can take over the second - a similar one. If they are different, any defect in the DNA chain leads to genetic failures. And in the end — to reduce life.
There are other explanations. For example, the hypothesis of a "toxic Y chromosome". American biologists have discovered that in the fruit fly Drosophila, the "male" Y chromosome affects the activity of genes of other chromosomes and contributes to the appearance of harmful mutations.
Another biological mechanism that, according to scientists, may be responsible for premature aging of men is cellular mosaicism, which is expressed in the fact that cells have different genotypes due to mutations. Over time, some chromosomes are greatly rearranged, others disappear altogether.
Back in the 1960s, doctors, counting the number of chromosomes in human leukocytes, noticed a strange phenomenon. In men, Y-chromosome deficiency increases with age in blood cells. The syndrome of her mosaic loss (mosaic loss of Y chromosome — mLOY) is observed in about one in five men after 60 years and in 40 percent of those over seventy.
Later it was found out that this has serious health consequences — the degree of mosaic loss of the "male" chromosome directly correlates with a high risk of age-related diseases and cancer, as well as a general reduction in life span. However, until recently it was unclear how the loss of the Y chromosome in leukocytes leads to damage to internal organs.
Of the 20 main causes of death, 16 reduce the life expectancy of men to a greater extent than women. WHO / World Health Statistics 2019
Missing chromosome
In a new study simulating the state of mLOY in mice, biologists from the USA, Japan and Sweden have analyzed at the cellular level the mechanism that leads to a change in the tissue of the heart muscle. Using the CRISPR-Cas9 gene editing tool, they constructed mice without Y chromosomes in leukocytes. And for a certain time, their indicators were compared with animals from the control group.
As it turned out, genetically modified individuals died earlier, and at autopsy they were diagnosed with cardiac fibrosis — a condition in which tissues become more rigid. As a rule, this leads to heart failure.
In humans, fibrosis usually occurs as a reaction to inflammation, but the experimental mice did not have it. The proliferation of connective tissue with the appearance of scarring changes, the same as in systemic aging, manifested itself in other organs, as well as throughout the body of animals.
Researchers believe that the loss of the Y chromosome accelerated the development of age-related diseases, made mice more prone to scarring on the heart and led to an earlier death.
To understand whether these findings can be extended to humans, the authors analyzed data from the British Biobank, a long—term observational study in which they collected genetic and medical information from about half a million Englishmen. Mosaic loss of the Y chromosome in blood cells really turned out to be the main risk factor for heart failure and heart fibrosis in men.
The cure for aging
The authors hope that thanks to their discovery, in the future they will create a method of treating mLOY based on personalized drugs adapted to specific mutations. By blocking the signaling pathway associated with Y-chromosome deficiency, the researchers partially reversed the fibrous changes in the modified mice.
According to scientists, existing antifibrotic drugs can become a more universal remedy. One of them, commonly used for the treatment of idiopathic pulmonary fibrosis, is currently undergoing clinical trials in the United States for the treatment of heart failure.
In the meantime, the authors recommend at least giving up tobacco, since smoking men are three times more likely to lose the Y chromosome in blood cells than non-smokers.
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