Machine-Readable Science • ISSN 3054-3991

Y Chromosome Loss: Systematic Review with ☸️SAIMSARA

Name: SAIMSARA Evidence Object longevity::Y_CHROMOSOME_LOSS_SS
Creator: SAIMSARA
License: https://saimsara.com/license/

Longevity & Public Health

Issue 2, Volume 1, 2026

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DOI: 10.62487/saimsaraab15307b

Editorial note

• Last update: 2026-04-27 09:00:24

What is this paper about

Y chromosome loss emerges in this paper not as a passive marker of ageing, but as a potentially central male-specific biological signal linked to cardiovascular death, cancer progression, neurodegeneration, and immune dysfunction across a massive evidence base. The full paper is worth reading because it shows where this signal is strongest, how consistent it is across 1,048 original studies, and why LOY may become both a prognostic biomarker and a future therapeutic target.

Human-verified editorial review Verified by World ID proof-of-human. This editorial layer was submitted from a SAIMSARA account verified as a unique human.

Abstract: This paper aims to systematically review and synthesize the current academic understanding of Y chromosome loss, identifying its prevalence, associated pathologies, underlying mechanisms, and clinical and research implications. The review utilises 1048 original studies with 5855590 total participants (naïve ΣN). Loss of the Y chromosome (LOY) is a prevalent, age-related genomic alteration in men, profoundly influencing health outcomes across a spectrum of diseases. This systematic review highlights LOY as a significant risk factor for increased mortality, particularly from cardiovascular events, with substantial LOY associated with a 68% higher risk of myocardial infarction. It is implicated in the pathogenesis and prognosis of numerous cancers, neurodegenerative disorders, and other systemic conditions, often by modulating immune responses and cellular metabolism. While many studies are correlational, the consistent associations underscore the importance of LOY in male-specific disease biology. A key limitation is the frequent lack of long-term prospective data, necessitating future large-scale cohort studies to definitively establish causality and validate LOY as a robust prognostic and therapeutic biomarker.

Keywords: Loss of Y chromosome; Mosaic LOY; Cancer; Tumor progression; Alzheimer's disease; Clonal hematopoiesis; Cardiovascular disease; Myocardial infarction; Amyotrophic lateral sclerosis

Review Stats

Generated: 2026-02-28 01:19:24 CET
Plan: Pro (expanded craft tokens; source: Europe PMC)
Source: Europe PMC
Scope: Titles/Abstracts (tiab)
Keyword Gate: Fuzzy (≥60% of required terms, minimum 2 terms matched in title/abstract)
Total Abstracts/Papers: 1795
Downloaded Abstracts/Papers: 1795
Included original Abstracts/Papers (all): 1422
Included original Abstracts/Papers (OSMA; excl. Mixed): 1048
Reference Index (links used in paper): 95
Total study participants (naïve ΣN): 5855590

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Reference Index (95)

[1] Lost but not least: Y chromosome loss as a driver of cancer. — https://doi.org/10.1016/j.trecan.2025.11.009
[2] Clinicopathological significance of loss of Y chromosome in male meningiomas. — https://doi.org/10.1002/path.70040
[3] HSATII RNA-dependent triplex formation in early human embryogenesis as a potential mechanism for Y chromosome loss in Turner syndrome. — https://doi.org/10.3389/fmolb.2025.1731956
[4] Loss of Y chromosome in Alzheimer's patients co-occurs with somatic mutations beyond CHIP drivers. — https://doi.org/10.26508/lsa.202503533
[5] Loss of the Y chromosome in bladder cancer drives metabolic reprogramming — https://doi.org/10.1101/2025.08.26.672471
[6] Catch Me If You Can: Could Y Chromosome Loss Spread in Cancer? — https://doi.org/10.1158/0008-5472.can-25-3058
[7] Evaluation of Loss of the Y Chromosome in Peripheral Blood as a Biomarker for Prostate Cancer. — https://doi.org/10.1002/pros.70128
[8] MosCoverY: A method to estimate mosaic loss of Y chromosome from sequencing coverage data. — https://doi.org/10.1016/j.ajhg.2025.08.016

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