- As we age, our strength and mobility decrease, largely due to muscle loss.
- Exercise, particularly resistance training, is widely recommended to help maintain muscle mass during aging.
- Now, a study has discovered how exercise acts at a molecular level to prevent muscle loss as we get older.
- Researchers have found that exercise restores muscle growth by inhibiting a pathway that leads to muscle deterioration and activating proteins that encourage repair.
From age 30, a person’s muscle mass decreases by 3-8% per decade, and this decline accelerates after age 60. Although muscle loss cannot be prevented entirely, we know that an active lifestyle, including strength training, can slow the decline and increase muscle strength, helping people remain mobile and independent for as long as possible.
Now, researchers have uncovered the molecular pathway that explains how exercise helps us maintain muscle.
The study, published in PNAS, found that exercise suppresses a transcription factor, DEAF1, that drives protein imbalance and muscle decline, helping muscles to regenerate.
“We believe our findings are important because they uncover a previously unknown biological mechanism that helps explain why muscles weaken with age. While it has long been known that exercise protects muscle health, the molecular reasons behind this benefit were not fully understood. Our study identifies DEAF1 as a key driver of age-related muscle decline and shows that exercise can directly suppress this pathway.”
— Tang Hong-Wen, Corresponding Author, Assistant Professor at Duke-NUS Medical School in Singapore.
Sebnem Unluisler, genetic engineer at the London Regenerative Institute, who wasn’t involved in the study, called the study highly significant, telling Medical News Today:
“It shows that aging shifts muscle protein regulation away from repair toward accumulation, which is a core driver of muscle decline. The transcription factor DEAF1 increases with age and suppresses the cell’s ability to clear damaged proteins, leaving muscle tissue less resilient and more fragile.”
The researchers examined a pathway controlled by the mTORC1 complex, which links nutrient signals to the metabolic processes required for cell growth. They knew that hyperactivation of mTORC1 leads to age-related muscle loss, but wanted to find out why.
To do this, they used fruit fly and mouse models to investigate what was controlling mTORC1, discovering that a protein, DEAF1, was key. Although DEAF1 is present in both young and older muscles, aging muscles are much more sensitive to its effects.
Tang Hong-Wen told Medical News Today:
“As we get older, our muscle cells slowly lose their ability to clear away damaged proteins and repair themselves. We discovered that a protein called DEAF1 becomes more active in aging muscle and drives another system, mTOR, into overdrive. This makes muscle cells focus too much on growth and not enough on maintenance and repair, which gradually leads to muscle weakness.”
“Exercise turns on protective ‘longevity’ genes called FOXO, which act like a brake on DEAF1. When DEAF1 is switched down, muscle cells regain their ability to recycle damaged parts and stay healthy. In simple terms, exercise helps restore balance inside muscle cells and keeps muscles stronger for longer,” Tang explained.
Both DEAF1 and mTORC1 regulate protein synthesis, autophagy (cell recycling), and metabolism. The researchers found that aging muscle is more sensitive to DEAF1 than younger muscle, so it loses its ability to clear damaged proteins and cellular components.
By exercising, you can activate FOXO genes, which regulate DEAF1, allowing the muscle to clear damaged material and focus on producing the proteins needed for muscle repair.
“Exercise counteracts [muscle decline] by down-regulating DEAF1 and re-activating cellular repair and quality-control mechanisms. In simple terms, exercise restores the muscle cell’s ability to fix itself rather than just produce new material. Resistance-based exercise is likely the most effective, as it provides the strongest molecular stimulus for repair, adaptation, and long-term maintenance of muscle integrity during aging.”
— Sebnem Unluisler
The researchers found that different exercises have different effects, but that any exercise can help to preserve and strengthen muscle.
Acute or resistance exercise, such as weight training, stimulates mTORC1 to promote muscle protein synthesis, whereas aerobic activity, such as brisk walking or cycling, suppresses the pathway by activating FOXO, which represses DEAF1 and prevents muscle degeneration.
“Our findings suggest that both aerobic (endurance) exercise and resistance (strength) training are beneficial for muscle health. Each type of exercise activates the body’s protective FOXO pathway in slightly different ways, and doing a combination of both is likely to provide the greatest benefit. In practical terms, regular physical activity — such as brisk walking, cycling, swimming, along with light weight or bodyweight training — can play an important role in maintaining strong, healthy muscles as we age.”
— Tang Hong-Wen
“One encouraging message from our study,” says Tan, “is that it is never too late to benefit from exercise. Even in older muscle, this protective pathway can still be switched on. We hope our findings will motivate more people to stay active and also help guide the development of new treatments that support healthy aging.”
“Our work also highlights that muscle aging is not simply about losing muscle mass, but about losing the ability to maintain healthy muscle,” he told us. “By identifying DEAF1 as a central regulator of this process, we aim to inspire new strategies — including both exercise-based and medical approaches — to help older adults remain stronger, more mobile, and more independent for longer.”
