Researchers have uncovered a key biological mechanism that explains why muscles become weaker with age and why regular exercise remains one of the most effective ways to preserve muscle strength. The findings identify a gene called DEAF1 as a major driver of age-related muscle decline and suggest it could become a promising target for future therapies.
The study found that as people age, levels of DEAF1 increase, causing an important muscle-growth pathway known as mTORC1 to become overactive. While mTORC1 normally supports muscle growth and repair, excessive activity disrupts the removal of damaged proteins, leading to their accumulation inside muscle cells and contributing to progressive muscle weakness.
Researchers also discovered that exercise naturally reverses this process. Physical activity activates a group of longevity-related proteins called FOXO, which suppress DEAF1, restore normal mTORC1 activity, and enable aging muscles to clear damaged proteins more efficiently. This helps muscles repair themselves and maintain strength as they age.
To validate their findings, scientists conducted experiments in aging mice. Animals that exercised showed significantly lower DEAF1 levels and healthier muscle function compared with sedentary mice. However, when DEAF1 levels became excessively high or FOXO activity was severely reduced, exercise alone was less effective, helping explain why some older adults benefit more from physical activity than others.
The researchers believe the newly identified FOXO–DEAF1–mTORC1 pathway could pave the way for therapies that mimic some of the biological benefits of exercise. Such treatments may help preserve muscle mass and function in older adults, as well as in patients recovering from illness, surgery, or chronic conditions that limit physical activity.
