Technical University of Munich Researchers Discover Mechanism Behind Female-Specific Aging Health Conditions

Technical University of Munich Researchers Discover Mechanism Behind Female-Specific Aging Health Conditions

(IN BRIEF) A team at the Technical University of Munich has uncovered a potential new explanation for sex-based differences in age-related diseases. Their study found that as female mice age, genes on the silenced second X chromosome become active again. This reactivation could play a role in both the positive and negative health effects seen in aging women, providing a new perspective on why women experience different disease outcomes compared to men.

(PRESS RELEASE) MUNICH, 28-May-2025 — /EuropaWire/ — Researchers at the Technical University of Munich (TUM) have proposed a new explanation for the sex differences observed in age-related diseases such as cardiovascular conditions and neurodegenerative disorders like dementia and Parkinson’s disease. Their findings reveal that in aging female mice, genes on the previously silenced second X chromosome become active again. This mechanism could help explain why women experience different health outcomes as they age.

In female mammals, one of the two X chromosomes is usually inactivated and forms the Barr body, a compact structure that prevents gene activity. This process is crucial to ensure that women, with their two X chromosomes, do not have double the gene expression seen in men, who carry only one X and one Y chromosome. However, some genes escape this inactivation and continue to function, potentially influencing disease development.

For the first time, the TUM team demonstrated that with increasing age, a larger number of genes escape inactivation on the X chromosome. Dr. Daniel Andergassen, group leader at the Institute of Pharmacology and Toxicology at TUM, explained, “As animals age, more and more genes escape the inactivation of the Barr body.” This discovery, published in Nature Aging, suggests that this reactivation could play a significant role in women’s health.

Aging Triggers Reactivation of Genes

The researchers studied the major organs of mice at various life stages. They found that in older mice, the proportion of genes escaping X-inactivation was about twice as high as in adults—reaching 6 percent, compared to just 3 percent in younger animals. In some organs, like the kidneys, the rate was even higher, with nearly 9 percent of genes becoming active. “As mice age, epigenetic processes loosen the tightly packed structure of the inactive X chromosome,” said Sarah Hoelzl, the study’s lead author. This loosening occurs primarily at the ends of the chromosome, allowing previously silenced genes to be expressed.

Impact on Disease

Interestingly, many of the genes reactivated with age are associated with disease. While this finding was based on mice, the X chromosome’s similarity in humans suggests that the same process could occur in aging women. The researchers believe that the reactivated genes might have both positive and negative effects. For example, the ACE2 gene, which becomes active in the lungs with age, could help mitigate pulmonary fibrosis. On the other hand, the increased activity of TLR8 in older mice might contribute to autoimmune diseases like late-onset lupus.

A New Perspective on Sex Differences in Disease

Dr. Andergassen emphasized that “Sex differences in age-related disease are incredibly complex.” Until now, most scientific explanations have focused on hormones and lifestyle factors. While some previous studies have examined escape genes on the X chromosome, the discovery that many genes on the inactive X can reactivate with age opens up new avenues of research. This insight could provide an alternative to hormonal explanations and deepen our understanding of why women tend to live longer than men.

Publications

Hoelzl, S., Hasenbein, T.P., Engelhardt, S., Andergassen, D. Aging promotes reactivation of the Barr body at distal chromosome regions. Nat Aging (2025). DOI:10.1038/s43587-025-00856-8

Media Contacts:

Corporate Communications Center

Paul Hellmich
paul.hellmich@tum.de
presse@tum.de

Contacts to this article:

Dr. Daniel Andergassen
Technical University of Munich
Institute of Pharmacology and Toxicology
Tel. +49 89 4140-3298
daniel.andergassen@tum.de
https://www.andergassenlab.com

SOURCE: Technical University of Munich