losing your y chromosome--9/16/26

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Today's selection -- from Beyond Inheritance by Roxanne Khamsi. As men age, some lose their Y chromosome:

“At the time, one of the main methods that scientists had to assess the genetic integrity of a cell was to simply stain it with a dye and then peer into a microscope to count how many chromosomes it possessed. The chromosomes appeared as deeply hued squiggles on the glass microscope slides. Each cell in regular tissue in the body normally contains forty-six chromosomes. Jacobs, who worked at the UK's Medical Research Council, had every reason to expect this number when she evaluated blood cells from almost a hundred healthy people ranging in age from five months to eighty-two years. None of these study participants had ever received X-ray treatment, which can cause genetic damage. Their chromosome count should have been normal. But when she and her collaborators analyzed the cells, they saw a strange trend: Some of them had entire chromosomes missing, and this was especially true of those from older individuals. 

“Two years later another study came out from Jacobs and other scientists at the same research institute, including the epidemiologist Richard Doll, who famously linked smoking to cancer. In this follow-up, the team determined that the chromosomes people would lose in some of their cells as they got older were often their sex chromosomes: In other words, women would lose an X chromosome and men would lose their Y chromosome. The latter, known as ‘loss of Y chromosome,’ received more attention, which is perhaps unsurprising given that medical research has historically focused more on men. 

“Within a couple of decades, scientists began to connect loss of Y with disease. The first study to do so was published in 1985. In the experiment, researchers examined the genetic integrity of bone marrow cells taken from patients with a kind of cancer called acute myeloid leukemia. They found that loss of Y was present in the patients they examined, and the condition seemed to revert back to normal in those whose cancer was successfully treated. 

“It's tempting to see data like that and presume that losing the Y chromosome causes cancer. But it's best not to leap to that assumption. 

G-banding patterns of human Y chromosome

“The truth is, chromosomal loss might simply be a red herring. A study of genetic data from more than two hundred thousand men in the UK uncovered a twist: It seems that other gene mutations might be at the root of both loss of Y and cancer. The analysis found more than 150 DNA variations associated with Y-chromosome loss and discerned that many of them were located near cancer-susceptibility genes. Notably, the variants linked to loss of Y were also correlated to cancers affecting the brain, kidneys, and other organs in both the men and women in the study. Women do not have any Y chromosomes to lose, so it's unlikely that the disappearance of this chromosome is to blame for the malignancies. Scientists believe that DNA changes such as the 150 variants they identified might make a cell prone to genetic instability–which, in turn, could result either in the accidental discarding of a chromosome or in DNA errors that turn a cell malignant. In other words, perhaps loss of Y and cancer simply share a root cause. 

“Despite the uncertainty about whether loss of Y is a cause of disease or is simply along for the ride, interest in the phenomenon has continued. Loss of Y has now been associated with a myriad of problems ranging from diabetes to Alzheimer's disease to a shorter lifespan. 

“There's also a better understanding of how frequently this chromosome goes AWOL in men as they head toward their golden years. The study of two hundred thousand men in the UK found that the proportion of participants with significant loss of Y rose from 3 percent at age forty to 44 percent among those at age seventy. According to some scientists, it is the most common mutation of any kind to arise after birth in men. Loss of Y can also be extraordinarily pervasive within the body: A small study found that one man was missing this chromosome in almost 90 percent of his sampled blood cells. 

“How do cells missing a chromosome become so abundant? When Jacobs and her coauthors published their findings decades ago, they put forward a few theories. One possibility, they wrote, was that dividing cells in older people are more likely to make mistakes when sorting their chromosomes. Or, perhaps, cells with an abnormal chromosome count somehow stick around. When it comes to loss of Y specifically, scientists have speculated that the Y chromosome may carry a growth suppressing gene, so jettisoning the chromosome would free a cell from that constraint. There is also the possibility that cells undergoing some other change that gives them an advantage might coincidentally drop their Y chromosome in the process. 

“Although less is known about loss of X–in which one of the two X chromosomes that women carry starts disappearing from their cells–there's an inkling that it's common, too. Jacobs is one of the few scientists to publish about this. In 2007, she coauthored a study of almost twenty thousand cells from more than 650 girls and women that detailed a ‘highly significant’ relationship between the X chromosome's disappearance and aging. Whereas around 0.07 percent of girls younger than age sixteen showed X chromosome loss, the number climbed to 7.3 percent of women by age sixty-five. (Sadly, the number of published papers related to this phenomenon in women remains paltry.) 

“There's still plenty more mystery to unravel about loss of Y and the disappearance of the X chromosome. But one thing is becoming clear: Even if people seem perfectly healthy as they grow older, there can be populations of abnormal cells taking hold in their bodies."

author:	Roxanne Khamsi
title:	Beyond Inheritance: Our Ever-Mutating Cells and a New Understanding of Health
publisher:	Riverhead Books
date:	Copyright 2026
pages:	82-84