{"id":5030,"date":"2022-07-16T13:04:14","date_gmt":"2022-07-16T17:04:14","guid":{"rendered":"https:\/\/med.virginia.edu\/cphg\/?p=5030"},"modified":"2022-12-05T13:08:39","modified_gmt":"2022-12-05T18:08:39","slug":"cphgs-josyf-mychaleckyj-collaborates-on-uva-research-that-might-explain-why-men-die-sooner","status":"publish","type":"post","link":"https:\/\/med.virginia.edu\/genome-sciences\/2022\/07\/16\/cphgs-josyf-mychaleckyj-collaborates-on-uva-research-that-might-explain-why-men-die-sooner\/","title":{"rendered":"CPHG’s Josyf Mychaleckyj Collaborates on UVA Research that Might Explain Why Men Die Sooner"},"content":{"rendered":"
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The loss of the male sex chromosome as many men age causes the heart muscle to scar and can lead to deadly heart failure, new research from the University of Virginia School of Medicine shows. The finding may help explain why men die, on average, several years younger than women.<\/p>\n

UVA researcher Kenneth Walsh says the new discovery suggests that men who suffer Y chromosome loss \u2013 estimated to include 40% of 70-year-olds \u2013 may particularly benefit from an existing drug that targets dangerous tissue scarring. The drug, he suspects, may help counteract the harmful effects of the chromosome loss \u2013 effects that may manifest not just in the heart, but in other parts of the body as well.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n

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UVA researcher Kenneth Walsh is involved in project that may explain why men, on average, die about five years before women. (Photo by Dan Addison, University Communications)<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n
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On average, women live five years longer than men in the United States. The new finding, Walsh estimates, may explain nearly four years of the five-year difference.<\/p>\n

\u201cParticularly past age 60, men die more rapidly than women. It\u2019s as if they biologically age more quickly,\u201d said Walsh, the director of UVA\u2019s Hematovascular Biology Center. \u201cThere are more than 160 million males in the United States alone. The years of life lost due to the survival disadvantage of maleness is staggering. This new research provides clues as to why men have shorter lifespans than women.\u201d<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n

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Chromosome Loss and Heart Health<\/h3>\n
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\"An<\/span>Scientists have long known some men lose Y chromosomes as they get older, but believed it was just a part of the aging process. UVA research suggests that loss of chromosomes can scar the heart and lead to earlier death. (UVA School of Medicine illustration)<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/article>
<\/figcaption><\/figure>\n

While women have two X chromosomes, men have an X and a Y. But many men begin to lose their Y chromosome in a fraction of their cells as they age. This appears to be particularly true for smokers. The loss occurs predominantly in cells that undergo rapid turnover, such as blood cells. (Loss of the Y chromosome does not occur in male reproductive cells, so it is not inherited by the children of men who exhibit Y chromosome loss.) Scientists previously observed that men who suffer Y chromosome loss are more likely to die at a younger age and suffer age-associated maladies such as Alzheimer\u2019s disease. Walsh\u2019s new research, however, is believed to be the first hard evidence that the chromosome loss directly causes harmful effects on men\u2019s health.<\/p>\n

Walsh, of UVA\u2019s Division of Cardiovascular Medicine and Robert M. Berne Cardiovascular Research Center, and his team used cutting-edge CRISPR gene-editing technology to develop a special mouse model to better understand the effects of Y chromosome loss in the blood. They found that the loss accelerated age-related diseases, made the mice more prone to heart scarring and led to earlier death. This wasn\u2019t the result of just inflammation, the scientists determined. Instead, the mice suffered a complex series of responses in the immune system, leading to a process called fibrosis throughout the body. This tug-of-war within the immune system, the researchers believe, may accelerate disease development.<\/p>\n

The scientists also looked at the effects of Y chromosome loss in human men. They conducted three analyses of data compiled from the UK Biobank, a massive biomedical database, and found that Y chromosome loss was associated with cardiovascular disease and heart failure. As chromosome loss increased, the scientists found, so did the risk of death.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n

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Potential Treatment<\/strong><\/h3>\n

The findings suggest that targeting the effects of Y chromosome loss could help men live longer, healthier lives.<\/p>\n

Walsh notes that one potential treatment option might be a drug, pirfenidone, that has already been approved by the federal Food and Drug Administration for the treatment of idiopathic pulmonary fibrosis, a form of lung scarring. The drug is also being tested for the treatment of heart failure and chronic kidney disease, two conditions for which tissue scarring is a hallmark. Based on his research, Walsh believes that men with Y chromosome loss could respond particularly well to this drug, and other classes of antifibrotic drugs that are being developed, though more research will be needed to determine that.<\/p>\n

At the moment, doctors have no easy way to determine which men suffer Y chromosome loss. Walsh\u2019s collaborator Lars A. Forsberg, of Uppsala University in Sweden, has developed an inexpensive polymerase chain reaction, or PCR, test (like those used for COVID-19 testing) that can detect Y chromosome loss, but the test is largely confined to his and Walsh\u2019s labs. Walsh, however, can foresee that changing: \u201cIf interest in this continues and it\u2019s shown to have utility in terms of being prognostic for men\u2019s disease and can lead to personalized therapy, maybe this becomes a routine diagnostic test,\u201d he said.<\/p>\n

\u201cThe DNA of all our cells inevitably accumulate mutations as we age,\u201d said Walsh, a member of UVA\u2019s Department of Biochemistry and Molecular Genetics. \u201cThis includes the loss of the entire Y chromosome within a subset of cells within men. Understanding that the body is a mosaic of acquired mutations provides clues about age-related diseases and the aging process itself.<\/p>\n

\u201cStudies that examine Y chromosome loss and other acquired mutations have great promise for the development of personalized medicines that are tailored to these specific mutations,\u201d Walsh said.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n

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Findings Published<\/strong><\/h3>\n

The researchers have published their findings in the journal Science<\/a>. The team consisted of Soichi Sano, Keita Horitani, Hayato Ogawa, Jonatan Halvardson, Nicholas W. Chavkin, Ying Wang, Miho Sano, Jonas Mattisson, Atsushi Hata, Marcus Danielsson, Emiri Miura-Yura, Ammar Zaghlool, Megan A. Evans, Tove Fall, Henry N. De Hoyos, Johan Sundstr\u00f6m, Yoshimitsu Yura, Anupreet Kour, Yohei Arai, Mark C. Thel, Yuka Arai, Josyf C. Mychaleckyj<\/strong>, Karen K. Hirschi, Forsberg and Walsh.<\/p>\n

Forsberg is a co-founder and shareholder of Cray Innovation AB.<\/em><\/p>\n

Link to Article here<\/a>.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

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