Y-chromosome loss due to aging

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?

Sex gap in aging and longevity: can sex chromosomes play a role? | Biology of Sex Differences | Full Text (2018

“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?


“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

“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.”

I think researchers, after many hours of watching YouTube videos) have identified the key reason women live longer: :wink:

@rivasp12 I moved your response from other thread here to keep it clean.

This is tricky.
Many of the HSC’s have probably also lost their Y’s but if you have Some that have retained their chromosomes then it may be possible with blood donations. Of course, it would only replace RBC’s and not the WBC’s.

This is such a new rabbit hole, and don’t think it’s interventionable. If smoking cessation can improve, what ELSE? Or is this one of those preordained genetic determinants?

Genetic variants associated with mosaic Y chromosome loss highlight cell cycle genes and overlap with cancer susceptibility (2017)

“We used genotype-array-intensity data and sequence reads from 85,542 men to identify 19 genomic regions that are associated with mLOY. Cumulatively, these loci also predicted X chromosome loss in women. We highlight the shared genetic architecture between mLOY and cancer susceptibility, in addition to inferring a causal effect of smoking on mLOY. Collectively,
our results demonstrate that genotype-array-intensity data enables a measure of cell cycle efficiency at population scale and identifies genes implicated in aneuploidy, genome instability and cancer susceptibility”

Mosaic loss of chromosome Y promotes leukemogenesis and clonal hematopoiesis (2021)

“Mosaic loss of chromosome Y (mLOY) in blood cells is one of the most frequent chromosome
alterations in adult males. It is strongly associated with clonal hematopoiesis, hematopoietic
malignancies, and other hematopoietic and nonhematopoietic diseases. However, whether there
is a causal relationship between mLOY and human diseases is unknown. our study validates mLOY as a functional driver for clonal hematopoiesis and leukemogenesis.”

“Less than 1% of the population under age 40 but approximately 10-20% of the population over age 70 has observable clonal hematopoiesis. Clonal hematopoiesis does not typically give rise to noticeable symptoms, but does lead to increased risk of cardiovascular disease”

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Unfortunately, I don’t feel like we can successfully intervene here. Well ,I guess a bone marrow transplant would do it, and then we could take rapamycin.

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