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NOBEL PRIZE 2026

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NIHNATIONAL INSTITUTE ON AGINGR01

Mosaic loss of Y chromosome in blood and heart failure

Completed
Institution
UNIVERSITY OF VIRGINIA, VA
Principal investigator
Kenneth Walsh
Funding
$399K
Duration
2021–2026
Open portfolio

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Abstract

SUMMARY Recent technological advances indicate that somatic DNA mutations accumulate with age and are remarkably prevalent. The accumulation of mutations in blood cells has been associated with increases in all-cause mortality and cardiometabolic diseases. Studies have focused on the precancerous clonal hematopoiesis state that results from mutations in “driver” genes that recurrently mutate in blood cancers. However, this class of mutations represent a small fraction of the total somatic mosaicism that occurs in blood. Mosaic loss of the Y chromosome (mLoY) in blood is the most common post-zygotic mutation in humans. Epidemiological studies have associated mLoY with all-cause mortality and a number of age-associated diseases. However, it is unknown whether there is a causal connection between mLoY and cardiovascular disease. Here, we will employ multiple murine models to assess the impact of mLoY in heart failure, and investigate this relationship at a mechanistic level.

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R01NATIONAL INSTITUTE ON AGINGIntegrative Myocardial Physiology/Pathophysiology A Study Section [MPPA]mutationsbloodmosaicheart failuresomaticall-cause mortalitychromosomeall-cause

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