A new study using the famed gene editing tool CRISPR to engineer mice that lose their Y chromosomes found that without Y chromosomes in their white blood cells, scar tissue builds up around their hearts, leading to heart failure and a shortened lifespan.
Errors in the human genome are a natural part of life. As we age and DNA replicates, small faults develop in our genes; eventually, some cells can end up losing entire chromosomes.
The genetic change mLOY (mosaic Loss Of Y Chromosome) affects at least 20 percent of 60-year-old men and 40 percent of 70-year-old men, according to researchers at the University of Virginia and Uppsala University in Sweden.
Although the Y chromosome has long been considered full of chunks of DNA not necessary for life, missing a Y chromosome has serious health consequences. In epidemiological studies, mLOY has been associated with ailments of aging like cancer and Alzheimer’s.
Now, mLOY could be linked to cardiac fibrosis, a scarring process common to most heart diseases. Since lack of Y was the sole cause of aging-related ailments in the mice, the study suggests that the same thing happens in humans. The authors of the new study say loss of Y could even account for some of the difference between the lifespans of men and women.
More research is needed before we can map out the direct consequences of mLOY in human since “Y-chromosome loss is a manifestation of broader genome instability,” according to University of Cambridge biologist John Perry. Age-related diseases are linked to a plethora of cellular processes gone awry and a host of genetic changes that have accumulated over time.
These revolutionary findings about losing Y in men raise the question, what about the two X chromosomes in women? And what about women with Turner syndrome, who are born with only one X chromosome?
Dr. Walsh said that women can lose an X chromosome as they age, but not as often as men lose their Y. More studies are needed, but so far, the UK Biobank data has not shown health risks for women who have lost an X.
On the other hand, women born with Turner syndrome share many of the same health risks as men who have lost their Y chromosomes — cardiovascular abnormalities and non-ischemic heart failure. Their average lifespan is shorter than women with two X chromosomes.
There is no way, besides to stop smoking, for men to protect themselves from losing Y (those in Dr. Walsh’s group found they could protect the hearts of mice by blocking the signaling pathway TGF-beta activated in the mice with Y chromosome-deficient cells).
Even though TGF-beta blocking drugs were somewhat effective in the mouse study, there is currently no evidence that these same drugs would be effective in men. For now, Dr. Stephen Chanock, the director of the division of cancer epidemiology and genetics at the National Cancer Institute, maintains that there is little purpose in testing for loss of Y: “the over-interpretation of these data for monetary purposes worries me deeply.”
Errors in the human genome are a natural part of life. As we age and DNA replicates, small faults develop in our genes; eventually, some cells can end up losing entire chromosomes.
The genetic change mLOY (mosaic Loss Of Y Chromosome) affects at least 20 percent of 60-year-old men and 40 percent of 70-year-old men, according to researchers at the University of Virginia and Uppsala University in Sweden.
Although the Y chromosome has long been considered full of chunks of DNA not necessary for life, missing a Y chromosome has serious health consequences. In epidemiological studies, mLOY has been associated with ailments of aging like cancer and Alzheimer’s.
Now, mLOY could be linked to cardiac fibrosis, a scarring process common to most heart diseases. Since lack of Y was the sole cause of aging-related ailments in the mice, the study suggests that the same thing happens in humans. The authors of the new study say loss of Y could even account for some of the difference between the lifespans of men and women.
More research is needed before we can map out the direct consequences of mLOY in human since “Y-chromosome loss is a manifestation of broader genome instability,” according to University of Cambridge biologist John Perry. Age-related diseases are linked to a plethora of cellular processes gone awry and a host of genetic changes that have accumulated over time.
These revolutionary findings about losing Y in men raise the question, what about the two X chromosomes in women? And what about women with Turner syndrome, who are born with only one X chromosome?
Dr. Walsh said that women can lose an X chromosome as they age, but not as often as men lose their Y. More studies are needed, but so far, the UK Biobank data has not shown health risks for women who have lost an X.
On the other hand, women born with Turner syndrome share many of the same health risks as men who have lost their Y chromosomes — cardiovascular abnormalities and non-ischemic heart failure. Their average lifespan is shorter than women with two X chromosomes.
There is no way, besides to stop smoking, for men to protect themselves from losing Y (those in Dr. Walsh’s group found they could protect the hearts of mice by blocking the signaling pathway TGF-beta activated in the mice with Y chromosome-deficient cells).
Even though TGF-beta blocking drugs were somewhat effective in the mouse study, there is currently no evidence that these same drugs would be effective in men. For now, Dr. Stephen Chanock, the director of the division of cancer epidemiology and genetics at the National Cancer Institute, maintains that there is little purpose in testing for loss of Y: “the over-interpretation of these data for monetary purposes worries me deeply.”
