Exercise has long been associated with healthier muscles, but scientists have now identified a biological mechanism that may explain its protective effects during ageing.

Researchers from Duke-NUS Medical School in Singapore, working with international collaborators, discovered that physical activity helps restore a cellular system responsible for removing damaged proteins and maintaining muscle function.

The findings, reported in October 2026 and published in Proceedings of the National Academy of Sciences in 2025, could eventually contribute to new treatments for age-related muscle deterioration.

Why Muscles Weaken With Age

As people grow older, muscle strength and function gradually decline, making everyday activities more challenging. At the cellular level, healthy muscles depend on a balance between producing new proteins and removing damaged ones.

A signalling pathway called mTORC1 helps regulate muscle growth and protein production. However, excessive mTORC1 activity can disrupt this balance, allowing damaged proteins to accumulate inside cells.

Over time, this process may contribute to muscle weakness and reduced recovery.

Scientists Identify A Key Gene

The researchers identified a gene called DEAF1 as an important regulator of muscle ageing. DEAF1 activity can increase with age, stimulating excessive mTORC1 activity and interfering with normal cellular maintenance. Under healthier conditions, proteins known as FOXOs help control DEAF1 and maintain the balance between protein production and removal.

As FOXO activity declines with age, DEAF1 may become overactive. This creates conditions in which muscle cells struggle to eliminate damaged components efficiently.

How Exercise Helps Muscles Recover

The study revealed that physical activity can help restore this disrupted process. Exercise activates regulatory mechanisms that reduce DEAF1 levels, allowing mTORC1 activity to return towards a healthier balance. Muscle cells can then remove damaged proteins more effectively while continuing to produce essential new ones. However, researchers identified an important limitation.

When DEAF1 becomes excessively elevated or FOXO activity declines too severely, exercise may be insufficient to restore normal muscle maintenance fully.

This could help explain why responses to exercise vary, although the mechanism has not yet been confirmed in humans.

What Animal Experiments Revealed

Scientists investigated the process using fruit flies and older mice. Increasing DEAF1 activity caused muscle function to deteriorate, while reducing its activity improved cellular maintenance and restored strength.

Similar findings across both animal models suggest that the mechanism has been preserved during evolution. Nevertheless, experiments in animals cannot establish whether targeting DEAF1 would produce equivalent results in people. Further research is required to confirm its relevance to human muscle health.

Could New Treatments Prevent Muscle Loss?

DEAF1 also influences muscle stem cells, which contribute to tissue repair after injury.

Researchers believe that regulating this gene could eventually support treatments for people experiencing age-related muscle weakness. Such approaches might be particularly valuable for individuals unable to exercise regularly because of illness, surgery or physical limitations. However, no treatment based on these findings has yet been established for humans.

The discovery provides a promising direction for future research while reinforcing the importance of physical activity in maintaining muscle health. Understanding how exercise supports cellular repair could eventually help more people preserve their strength, mobility and independence as they age.