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barbara hudson writes:

The Atlantic reports aging causes men to lose Y chromosomes [theatlantic.com].

Researchers have found men who are missing the Y chromosome in as many as 87 percent of cells in their blood.

The Y chromosome is the smallest one, and errors make it more likely that it will fail to replicate during cell division. When this happens, future generations of those cells also no longer have a Y chromosome.

The ongoing loss of Y chromosomes correlates with increases in cancer.

In (samples of) blood, loss of the Y chromosome in some cells is the most commonly observed mosaicism, but there are countless other examples. In women, some blood cells lose one X chromosome. Other subsets of blood cells might gain a mutation in just one gene, lose only a small bit of a chromosome, or even gain an entire chromosome. (Red blood cells don’t carry DNA at all, so this applies only to white blood cells.)

Perry and his colleagues also wanted to understand why the Y chromosome disappears in some men but not others. They looked into whether certain genetic variants on other chromosomes predisposed men one way or another, and they ended up finding 156 variants linked to Y-chromosome loss. Many are also near cancer-susceptibility genes, and having these same variants was correlated with higher risk of prostate and testicular cancer in men—as well as glioma, kidney, and other cancers in both men and women.

“That was, I think, the really interesting part,” says Siddhartha Jaiswal, a pathologist at Stanford who studies blood. It suggests that losing a Y chromosome is probably not the ultimate cause of bad health outcomes correlated with it, because the women never had a Y chromosome to lose. Rather, the same genetic variants that predispose someone to Y-chromosome loss might be also putting that person at risk for cancer. The two outcomes could have a common cause, because both are rooted in errors in DNA. Cancer is the result of many accumulated mutations that allow a cell to replicate out of control. Y-chromosome loss is one big glaring mutation. Perry suggests both could be the result of some hitch in the normal process of responding to and repairing DNA damage.“Y-chromosome loss is a manifestation of broader genome instability,” he says. In other words, the disappearing Y chromosome is a sign the body is allowing DNA errors to accumulate.

But why is the Y chromosome lost more frequently than others? It is the smallest chromosome and possibly the most dispensable. “Probably because it carries relatively few genes, its loss is tolerated better than others,” says David Steensma, an oncologist at Dana-Farber Cancer Institute. But the fact that Y-chromosome loss is so common, he says, also suggests it might confer some small advantage to the cells that have lost it. Researchers have found men who are missing the Y chromosome in as many as 87 percent of cells in their blood.

The case of prostate cancer is interesting. As men enter old age, they often end up with naturally higher levels of estrogen than women, as well as lower testosterone levels. This natural process might lower prostate cancer risk; men who take anti-androgens and estrogen to combat prostate cancer might just be giving nature a helping hand.

Original Submission