Daijiworld Media Network – Singapore
Singapore, Jul 7: Researchers have identified a molecular "switch" that helps explain how exercise keeps ageing muscles healthy, offering fresh insights that could pave the way for new treatments to prevent age-related muscle loss.
The study, led by researchers from Duke-NUS Medical School in collaboration with Singapore General Hospital and Cardiff University, found that physical activity lowers the levels of a gene called DEAF1, enabling ageing muscles to remove damaged proteins, repair themselves and maintain strength.
The findings, published in the Proceedings of the National Academy of Sciences (PNAS), shed light on the biological mechanisms behind muscle ageing and may help develop therapies that mimic the benefits of exercise for older adults.
Researchers explained that healthy muscles play a vital role not only in movement but also in regulating metabolism, maintaining blood sugar levels and supporting overall health. However, muscle strength naturally declines with age, increasing the risk of falls, fractures and slower recovery from illness or injury.
The study focused on mTORC1, a key growth pathway responsible for protein production and muscle maintenance. In ageing muscles, this pathway becomes overactive, causing muscles to prioritise building new proteins while becoming less efficient at removing damaged ones. As a result, damaged proteins accumulate within muscle cells, accelerating muscle deterioration.
The researchers identified the DEAF1 gene as a major contributor to this imbalance. They found that DEAF1 levels rise as muscles age, increasing mTORC1 activity and disrupting the balance between protein production and protein clearance.
Under normal conditions, DEAF1 is regulated by a group of proteins known as FOXOs. However, FOXO activity naturally declines with age, allowing DEAF1 levels to increase unchecked and reducing the muscles' ability to repair themselves.
According to the research team, exercise helps restore this balance by activating proteins that suppress DEAF1, enabling ageing muscles to eliminate damaged proteins, rebuild tissue and remain stronger and more resilient.
Assistant Professor Tang Hong-Wen, the study's lead author, said physical activity effectively corrects the imbalance by reducing DEAF1 levels and restoring the normal functioning of the muscle repair system.
However, the researchers also found that exercise may not be sufficient in every case. In muscles where DEAF1 levels become extremely high or FOXO activity falls sharply, exercise alone may not fully restore the muscles' repair capacity. This may explain why some older adults benefit more from exercise than others.
To validate their findings, the team conducted experiments using fruit flies and ageing mice. The results were consistent across both models, showing that increasing DEAF1 accelerated muscle weakening, while reducing its levels restored healthier protein balance and improved muscle strength.
The researchers believe the findings could have implications beyond normal ageing. DEAF1 also influences muscle stem cells responsible for repairing and regenerating muscle tissue, suggesting that targeting the gene may help improve recovery after surgery, illness or chronic diseases such as cancer.
Research assistant and first author Priscillia Choy Sze Mun said lowering DEAF1 helps ageing muscles regain strength and balance, describing the process as similar to "hitting the rewind button" for muscle health.
Professor Patrick Tan, Senior Vice-Dean for Research at Duke-NUS Medical School, said the study provides a molecular explanation for why ageing muscles gradually lose their ability to repair themselves and how exercise restores that balance in many individuals. He added that identifying DEAF1 as a key regulator could eventually lead to therapies capable of reproducing some of the health benefits of exercise, particularly for rapidly ageing populations.