Kenneth Glad
Laboratory experiments have identified a gene that appears to interfere with protein maintenance in aging muscle. The discovery could help explain differences in exercise response, although the mechanism has not been confirmed in people.
Experiments involving fruit flies and older mice suggest that physical activity can restore part of the cellular maintenance process disrupted by aging.
Researchers from Duke-NUS Medical School, Singapore General Hospital and Cardiff University linked that effect to DEAF1, a gene that became increasingly active in older muscle tissue.
The study, published online in the Proceedings of the National Academy of Sciences on November 24, 2025, examined how DEAF1 affects mTORC1, a pathway involved in growth, protein production and muscle maintenance.
Higher DEAF1 activity increased mTOR expression and disrupted the balance between producing new proteins and removing damaged cellular material. The resulting decline in protein quality control contributed to worsening muscle function in the animal models.
DEAF1 disrupts cellular maintenance
FOXO proteins ordinarily help keep DEAF1 under control. As FOXO activity weakened with age, DEAF1 levels rose and mTORC1 became excessively active.
Exercise activated FOXO regulation and lowered DEAF1 when that regulatory system remained functional. This helped return mTORC1 activity to a healthier level and improved the removal of damaged proteins.
“Exercise can reverse this process, correcting the imbalance,” said Hong-Wen Tang, a Duke-NUS assistant professor and senior author of the study, according to ScienceDaily.
The outcome changed when researchers artificially increased DEAF1 or inhibited FOXO. Under those experimental conditions, exercise did not fully restore the maintenance system or deliver the same muscle benefits.
That result could offer one explanation for why the effects of exercise differ between individuals, although the study did not test older adults.
Animal models show similar effects
Across both animal models, altering DEAF1 changed how quickly muscle function deteriorated. Raising its activity accelerated weakness, while reducing it improved protein turnover and physical performance.
The results indicate that the pathway may operate across different species. They do not show that a treatment aimed at DEAF1 would be safe or effective in humans.
Priscillia Choy Sze Mun, the study’s first author and a Duke-NUS research assistant, said lowering the gene helped older muscles regain strength and balance.
The next step will be to establish whether DEAF1 plays the same role in human muscle and whether it can be modified without interfering with other essential biological processes.
Sources: Proceedings of the National Academy of Sciences; ScienceDaily
