How Exercise Reverses Muscle Aging

July 10, 2026

The research team, working with collaborators from Singapore General Hospital and Cardiff University, found that exercise helps correct an important imbalance that develops inside aging muscle cells. The findings, published in the Proceedings of the National Academy of Sciences (PNAS), provide new insight into the biological mechanisms behind muscle aging and could eventually lead to new approaches for preventing age related muscle loss.

Why Muscle Health Declines With Age Healthy muscles do far more than support movement. They also play important roles in metabolism, blood sugar regulation, and overall health. Beginning in middle age, muscle strength and function gradually decline, increasing the risk of falls, fractures, and slower recovery after illness or injury.

The consequences extend beyond individual health. As populations age, muscle loss can increase demands on caregivers and healthcare systems. Preserving muscle function is therefore an important part of maintaining independence and quality of life.

One of the key regulators of muscle health is a growth pathway called mTORC1, which helps control protein production and muscle maintenance. In aging muscles, this pathway can become excessively active. When that 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.

The researchers identified a gene called DEAF1 as an important factor behind this process.

According to the study, DEAF1 levels rise in aging muscles. As DEAF1 increases, it drives mTORC1 activity higher, disrupting the normal balance between protein production and protein removal. This imbalance accelerates muscle deterioration.

Under normal conditions, DEAF1 is regulated by a group of proteins known as FOXOs. However, FOXO activity naturally declines with age. As a result, DEAF1 is no longer kept under tight control, allowing its levels to increase and pushing muscles further away from repair and maintenance.

The team discovered that exercise can help reverse this imbalance, provided the underlying regulatory system remains responsive.

Assistant Professor Tang Hong-Wen from the Cancer and Stem Cell Biology Program at Duke-NUS, the study’s lead author, said: “Exercise can reverse this process, correcting the imbalance. Physical activity activates certain proteins which lower DEAF1 levels, bringing the growth pathway back into balance.

This allows aging muscles to clear out damaged proteins, rebuild themselves properly, and help them stay stronger and more resilient.” The researchers 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.