Men are losing their Y chromosomes – and it’s accelerating the ageing process ...Middle East

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Men are losing their Y chromosomes – and it’s accelerating the ageing process

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Hello, and welcome back to Everyday Science.

    Quick question: what is small, weird, and yet has been central to the lives of half the human race?

    The answer – if you didn’t guess from the picture, above – is the Y chromosome. This is part of human DNA that makes foetuses male.

    Along with a role in sperm production, this was once seen as more or less the only function of the Y chromosome.

    And yet recent research has found its story is more interesting than we thought. It has turned out to be surprisingly common for men’s cells to lose their Y chromosomes as they get older.

    This phenomenon seems to raise the risk of a host of medical conditions, including heart attacks, cancer and Alzheimer’s disease. The latest research suggests that in a way, it may even hasten the ageing process itself.

    Weird genetic garbage

    The explanation for many of the Y’s weird features lies in how sex is determined, so first we need a bit of background biology.

    DNA, present in nearly every cell in our body, is packaged into discrete bundles, called chromosomes. Humans have 23 pairs of chromosomes, with one inherited from their mum and the other from their dad.

    Most of these chromosomes are very similar, but not one pair, the sex chromosomes; women carry two X chromosomes, while men carry one X and one Y.

    The X is nearly three times the size of the Y chromosome, but the Y carries one very important gene; it is activated in seven-week-old embryos to kick off testicle formation.

    The Y chromosome may explain why some men seem to age better than others (Photo: Getty)

    It is because the X and Y, alone among the chromosomes, are different to each other, that there are several peculiarities about the Y.

    When DNA is duplicated before cell division, if mistakes arise, they can usually be eliminated in something like a copy-checking process, where one chromosome is compared to its partner.

    But because the Y is different to the X, it cannot be checked in this way, and so genetic mistakes have crept in during evolution.

    This is why the Y is full of genes with mutations that make them defunct and why it is among the smallest of our chromosomes, with many mutated genes having been jettisonned in the past.

    Scientists describe the Y as “genetic garbage”. Some have even predicted that over millions of years, it might dwindle to nothing, leading to the end of men.

    Goodbye Y

    In the present day, geneticists have noticed the Y chromosome may be absent from some of a man’s cells, especially in older men, with up to two in five men having detectable Y loss by age 70.

    Usually a cell dies if it loses a chromosome, but it was thought that because the Y’s main job is sex determination in the womb this phenomenon had no impact on adults.

    That changed in 2014, when Swedish scientists showed that Y loss in blood cells correlates with how long men live – those who have Y loss in some of their cells die five years sooner. Many further studies showed Y loss raises the risk of heart attacks or diseases such as cancer and Alzheimer’s.

    Correlation or causation?

    The problem with studies like these is they are a kind known as “observational”, which means scientists just observe patterns of disease incidence and some risk factor – in this case Y loss.

    Y loss could just be an innocent bystander, a marker of ageing, a bit like grey hair, but not be directly causing the health problems, said Professor John Perry, a geneticist at the University of Cambridge. “I’m always skeptical of any form of observational [study],” he said.

    The bystander theory was strengthened by Professor Perry’s 2019 research that found men are more likely to have Y loss if they have certain genes (carried by other, non-sex-determining, chromosomes) that make someone’s DNA copying machinery more prone to errors. Those genes could both lead to Y loss in immune cells, and separately lead to heart disease, cancer, and so on.

    “The theory is Y loss is just the manifestation of a whole lot of problems happening all over the place,” said Professor Perry. His work even showed that those same genes were linked with breast cancer in women – an effect that definitely couldn’t be happening through the Y chromosome, because it’s absent in women.

    Theory of ageing

    But since then, two other kinds of research have suggested this is wrong, and Y loss really is harmful after all. One was the creation of mice whose immune systems were replaced with cells lacking the Y chromosome, which developed heart disease. “This indicates its not just a bystander,” said Dr Lars Forsberg, a geneticist at Uppsala University in Sweden, who was involved in the work.

    The other sheds light on why Y loss could be involved in so many conditions. It concerns a theory that says most diseases of ageing arise because of the growing accumulation in our bodies of “senescent cells”, which have become damaged and are malfunctioning.

    Senescent cells are supposed to be killed off by our immune system. But in mice, immune cells that lack a Y chromosome are less able to do this, Dr Forsberg helped to show in August. “It showed how loss of Y can be associated with disease in so many different organs,” he said. “The immune system is not doing its proper job to remove senescent cells.”

    Professor Perry said the work in mice was elegant, but it didn’t show that Y loss was directly harmful for every disease it has been linked with by observational studies. “Different hypotheses could be true for different diseases,” he said.

    Reason for men’s shorter lives

    Men tend to be intrigued by Y chromosome research, but that may be due to misunderstandings, said Professor Perry. “People think about loss of Y chromosome in their body, and they think that that might influence masculinity in some way. But this is about the function of [immune] cells.”

    There are blood tests that can tell you if you have Y loss but there is no point for most men, and the only thing you can do to cut your risk of Y loss is follow health advice, like avoiding smoking and eating healthily.

    Men may now have even more reason to do so, however. Dr Forsberg has calculated from UK data that Y loss explains half of the difference in lifespan between men and women, with women living to 83 on average, and men 79. He presented preliminary results at the European Society for Human Genetics conference this year.

    If all else fails, scientists in the fields of ageing and longevity are getting increasingly interested in senescent cells, and are developing drugs to clear them from the body. If senescent cells really are behind the impact of Y loss, then one day, the treatment be as simple as a daily pill.

    I’ve also written

    In his new book, Warhead: How the brain shapes war and war shapes the brain, Dr Nicholas Wright argues that understanding how our brains are wired for threats could explain today’s high rates of mental health problems and even help alleviate them.

    “In our peaceful societies, because our brains are built to look out for life-threatening risks, they will find threats even where they don’t really exist,” he says. “Mental health conditions like anxiety are a natural consequence of the way our brains have evolved.”

    I’ve been reading

    I can’t stop browsing through The Wonder of Insects, a new book for nature lovers by zoologist Dr Ross Piper. This small but perfectly formed book is perfect for a nightstand.

    It isn’t an exhaustive textbook of entomology, but rather an insider’s tour guide through a branch of the animal kingdom that is at times intriguing, charming and sometimes dazzling.

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