The study found that exercise can help restore this balance. Physical activity activates proteins that reduce DEAF1 levels, allowing ageing muscles to improve their ability to remove damaged proteins, rebuild effectively and maintain strength
Exercise may hold the key to slowing age-related muscle decline, with scientists identifying a molecular “switch” that helps ageing muscles repair damage and maintain strength.
A new study by researchers at Duke-NUS Medical School, in collaboration with Singapore General Hospital and Cardiff University, has revealed that physical activity can restore repair mechanisms that weaken as muscles age. The findings, published in Proceedings of the National Academy of Sciences, provide new insight into the biological processes behind muscle ageing and could open the door to future treatments for age-related muscle loss.
Muscle health plays a crucial role beyond movement. Strong muscles support metabolism, help regulate blood sugar and contribute to overall wellbeing. However, from middle age onwards, muscle strength and function gradually decline, increasing the risk of falls, fractures and slower recovery from illness or injury.
The researchers found that a gene called DEAF1 plays a central role in this decline. As muscles age, DEAF1 levels rise, causing overactivity of a growth pathway known as mTORC1. While mTORC1 normally helps control protein production and muscle maintenance, excessive activation disrupts the balance between building new proteins and removing damaged ones.
Over time, the accumulation of damaged proteins places stress on muscle cells and contributes to weakening. Normally, DEAF1 is controlled by proteins called FOXOs, but FOXO activity declines with age, allowing DEAF1 levels to increase and reducing the muscle’s ability to repair itself.
The study found that exercise can help restore this balance. Physical activity activates proteins that reduce DEAF1 levels, allowing ageing muscles to improve their ability to remove damaged proteins, rebuild effectively and maintain strength.
“Exercise can reverse this process, correcting the imbalance,” said Assistant Professor Tang Hong-Wen from Duke-NUS, the study’s lead author. He explained that lowering DEAF1 helps bring the muscle growth pathway back into balance, enabling older muscles to become more resilient.
However, researchers noted that exercise may not have the same impact on everyone. In some older muscles, extremely high DEAF1 levels or severely reduced FOXO activity may limit the ability to recover fully. This could explain why some people experience greater benefits from exercise than others as they age.
To confirm their findings, scientists conducted experiments on fruit flies and older mice. The results showed that increased DEAF1 accelerated muscle weakening, while reducing the gene improved protein balance and muscle strength across both species.
The discovery could have wider medical applications. DEAF1 also affects muscle stem cells, which are responsible for tissue repair and regeneration. Targeting this pathway may eventually help people recovering from surgery, chronic illnesses or conditions such as cancer where muscle loss is a concern.
Researchers believe understanding DEAF1 could lead to new therapies that mimic some of exercise’s benefits at the molecular level, offering additional support for ageing populations.
“This study helps explain, at a molecular level, why ageing muscles lose their ability to repair themselves and why exercise can restore that balance,” said Professor Patrick Tan, Senior Vice-Dean for Research at Duke-NUS.
