Science Review Shows X and Y Chromosomes Shape Disease Risk Beyond Hormones
The review identifies sex chromosomes as active participants in lifelong health trajectories rather than passive sex determinants. It highlights Y loss as both biomarker and potential driver in multiple age-related diseases. Evidence remains largely observational with limited interventional data.
The review, co-led by Dan Theodorescu and Dena Dubal, draws on human cohort data, mouse models with parent-of-origin X tracking, and genomic assays to map how incomplete X inactivation and age-related Y loss alter gene dosage across tissues. Female cells can reactivate X-linked genes with advancing age, while male cells losing Y in blood show elevated risks for leukemia, heart failure, Alzheimer disease, and infections. These patterns emerge after controlling for hormone levels in multiple studies.
Theodorescu lab: At least three ongoing cancer immunotherapy trials will stratify enrollment by Y chromosome status within 24 months, with detectable differences in response rates exceeding 15%.
Sources (2)
- [1]Primary Source(https://medicalxpress.com/news/2026-09-sex-chromosomes-lifelong-health-biological.html)
- [2]Supporting Source(https://www.science.org/doi/10.1126/science.adq9231)