I had never heard of this aging pathway…yet another.
“Humans have X and Y sex chromosomes, with the XY combination being male and XX being female. However, as men age, they lose their Y chromosome, primarily in blood cells. This is called mosaic loss of Y chromosome in blood (mLOY). Men with mLOY are found to live shorter lives than men without mLOY, and they are thought to be more prone to Alzheimer’s disease, solid tumors such as prostate and colon cancer, and heart attacks, as well as strokes.”
Is this another reason for why women live longer?
“Recent data suggest that sex chromosomes may also contribute to the sex gap in aging/longevity through several potential mechanisms, including the unguarded X/Z, the toxic Y/W and the loss of Y/W.”
“A new study shows that men are genetically predisposed to dying younger because their Y chromosome is unable to protect an unhealthy X chromosome.”
For the docs out there, when we donate blood, do the stem cells rejuvenate blood cells with this recapitulated Y chromosome loss, or do a fresh reset?
https://www.science.org/doi/10.1126/science.abn3100#core-collateral-purchase-access
“Hematopoietic mosaic loss of Y chromosome (mLOY) is associated with increased risk of mortality and age-related diseases in men, but the causal and mechanistic relationships have yet to be established. Here, we show that male mice reconstituted with bone marrow cells lacking the Y chromosome display increased mortality and age-related profibrotic pathologies including reduced cardiac function. Cardiac macrophages lacking the Y chromosome exhibited polarization toward a more fibrotic phenotype, and treatment with a transforming growth factor β1–neutralizing antibody ameliorated cardiac dysfunction in mLOY mice. A prospective study revealed that mLOY in blood is associated with an increased risk for cardiovascular disease and heart failure–associated mortality. Together, these results indicate that hematopoietic mLOY causally contributes to fibrosis, cardiac dysfunction, and mortality in men.”
GWAS of mosaic loss of chromosome Y highlights genetic effects on blood cell differentiation
And how about women (XX) and loss of chromosome and aging?
Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome
https://www.nature.com/articles/ncomms11843/
“Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.”
