A groundbreaking study from Duke-NUS Medical School has shed new light on the long-standing question of why exercise is so effective in maintaining muscle strength as we age. Led by Assistant Professor Tang Hong-Wen, the research team has discovered a key reason behind the rejuvenating effects of physical activity on older muscles.

Healthy muscles play a vital role in our overall health, supporting not only movement but also metabolism, blood sugar regulation, and overall well-being. However, as we age, muscle strength and function gradually decline, increasing the risk of falls, fractures, and slower recovery after illness or injury.

The study found that exercise helps correct an important imbalance that develops inside aging muscle cells. The researchers identified a gene called DEAF1 as an important factor behind this process, which becomes excessively active in aging muscles. When this happens, muscles focus more on building new proteins while becoming less efficient at removing damaged ones.

Over time, these damaged proteins accumulate inside muscle cells, placing them under stress and contributing to the gradual loss of strength associated with aging. Until now, scientists did not fully understand what causes this imbalance. However, the research team discovered that exercise can help reverse this process, correcting the imbalance and allowing aging muscles to clear out damaged proteins, rebuild themselves properly, and stay stronger and more resilient.

The team also found an important limitation. In some older muscles, DEAF1 levels become extremely high or FOXO activity drops significantly. In those cases, exercise alone may not be enough to fully restore the muscle’s repair capacity. This finding may help explain why some older adults experience greater benefits from exercise than others and highlights the importance of understanding the underlying biology of muscle aging.

To test their findings, the researchers conducted experiments in both fruit flies and older mice. The results were consistent across both species, showing that raising DEAF1 levels caused muscles to weaken more rapidly, while lowering DEAF1 restored healthier protein balance and improved muscle strength. The findings suggest that DEAF1 plays a conserved role in muscle aging across different organisms.

The implications of the research may extend beyond normal aging. DEAF1 also influences muscle stem cells, which are responsible for helping muscles repair and regenerate tissue. These stem cells naturally become less effective with age, and disruptions in DEAF1 appear to make recovery even more difficult. The findings could also prove valuable for people recovering from surgery, illness, or chronic diseases such as cancer. Researchers suggest that targeting DEAF1 could potentially reproduce some of the beneficial effects of exercise at the molecular level, helping maintain muscle strength even when physical activity is limited.