Scientists at Duke-NUS Medical School in Singapore revealed on Tuesday, July 6, 2026, a crucial mechanism for combating muscle aging. They found that physical activity acts as a biological “reset button” for aging muscles, reestablishing their ability to repair themselves and maintain strength.

Research details the essential reason why exercise is so effective at preserving muscle vitality in older adults. The Duke-NUS Medical School study indicates that exercise can reactivate the body’s repair systems, which tend to weaken with age, helping with muscle recovery and maintaining functionality in old age.

Conducted in partnership with Singapore General Hospital and Cardiff University, the scientific team observed that exercise corrects a significant imbalance that forms in older muscle cells. The findings, released in the Annals of the National Academy of Sciences (PNAS), offer new insights into the biology of muscle aging and could pave the way for novel strategies to combat age-related muscle loss.

Deterioration of muscle health over the years

Beyond just sustaining movement, healthy muscles play a vital role in metabolism, blood sugar regulation, and overall body health. From middle age onwards, muscle strength and function progressively decrease, increasing the risk of falls, fractures and prolonging recovery from illness or injury.

The repercussions of this loss are not limited to individual health. With the increase in the elderly population, the decrease in muscle mass can place a burden on caregivers and healthcare systems. Maintaining muscle function is, therefore, essential for autonomy and quality of life in old age.

A growth signaling pathway known as mTORC1 is one of the key regulators of muscle health, controlling protein production and tissue maintenance. In aging muscles, this pathway can become overactive. When this occurs, muscles prioritize the synthesis of new proteins, becoming less efficient in eliminating damaged proteins.

Over time, the accumulation of these damaged proteins within muscle cells overloads them, contributing to the gradual loss of strength associated with aging. Until now, scientists were unclear about the exact cause of this imbalance.

DEAF1 emerges as a central gene in muscle aging

Researchers identified the DEAF1 gene as a crucial factor in this muscle aging process.

According to the study, DEAF1 levels increase in older muscles. This growth of DEAF1 intensifies mTORC1 activity, disrupting the normal balance between protein creation and removal. This imbalance, in turn, accelerates muscle deterioration.

Normally, DEAF1 is regulated by a group of proteins called FOXOs. However, FOXO activity naturally decreases with age. Thus, DEAF1 loses its tight control, which allows its levels to rise and further distance the muscles from their repair and maintenance capacity.

Physical exercise helps in muscle recovery

The team found that physical exercise can help reverse this imbalance, as long as the underlying regulatory system is still responsive.

Assistant Professor Tang Hong-Wen, lead author of the study and a member of the Cancer and Stem Cell Biology Program at Duke-NUS, explained: “Exercise can reverse this process, correcting the imbalance. Physical activity activates certain proteins that reduce DEAF1 levels, bringing the growth pathway back into balance. This allows aging muscles to eliminate damaged proteins, rebuild properly and remain stronger and more resilient.”

The researchers also pointed out an important limitation. In some older muscles, DEAF1 levels may become excessively high or FOXO activity may decrease considerably. In these scenarios, exercise alone may not be enough to fully restore the muscle’s repair capacity.

This finding may explain why not all older people benefit equally from exercise and highlights the importance of deepening our understanding of the biology behind muscle aging.

Animal tests confirm research results

To validate their findings, the scientists conducted experiments with fruit flies and older mice.

The results were consistent in both species. Increasing DEAF1 levels led to faster muscle wasting, while reducing this gene restored a healthier protein balance and improved muscle strength. Evidence suggests that DEAF1 has a conserved role in muscle aging in diverse organisms.

Implications of the discovery go beyond aging

The ramifications of this research could extend beyond ordinary aging.

The DEAF1 gene also affects muscle stem cells, which are crucial for the repair and regeneration of muscle tissue. These stem cells naturally become less efficient with age, and changes in the DEAF1 gene appear to further compromise recovery.

The findings could be equally valuable for individuals recovering from surgery, illness or chronic conditions such as cancer. The researchers indicate that manipulating the DEAF1 gene can potentially replicate some of the beneficial effects of exercise at a molecular level, helping to maintain muscle strength even when physical activity is restricted.

Priscillia Choy Sze Mun, research assistant in the Cancer and Stem Cell Biology Program at Duke-NUS and first author of the study, commented: “Physical exercise signals muscles that they need to ‘cleanse themselves and rebalance’. Reducing the expression of DEAF1 helps older people’s muscles regain strength and balance, almost like hitting the rewind button. With millions of older people at risk of muscle decline, understanding what DEAF1 is could lead to new ways of protect muscles and improve quality of life.”

Professor Patrick Tan, Senior Vice-Chancellor of Research at Duke-NUS, added: “This study helps explain, at a molecular level, why aging muscles lose the ability to regenerate and why exercise can restore this balance in some individuals. By identifying DEAF1 as a key regulator in this process, these findings could lead to new ways of bringing the benefits of exercise to societies with rapidly aging populations.”