Exercise May Help Aging Muscles Run a Better Cleanup Cycle

Key Takeaways

• Researchers identified a gene called DEAF1 that becomes more active in aging muscle and is linked to weaker repair and maintenance.

• Higher DEAF1 activity pushed a growth-related pathway, called mTORC1, into overdrive—favoring protein production while allowing damaged proteins to accumulate.

• In animal experiments, exercise lowered DEAF1 activity and helped restore the balance between making new proteins and clearing damaged ones.

• Reducing DEAF1 improved muscle strength in the study models, while increasing it weakened muscle function.

• The work was conducted in fruit flies and mice; it does not prove the same mechanism explains exercise benefits in people.

Healthy muscle depends on continuous maintenance. Cells need to make proteins for structure and repair, but they also need to remove proteins that are worn out or damaged.

The study points to a problem that can emerge with age: a cellular growth pathway called mTORC1 can become too active. When that happens, muscle cells may focus too heavily on production and lose ground on cleanup.

A Molecular Middleman

The researchers traced part of that imbalance to DEAF1. In older muscle, rising DEAF1 activity appeared to drive mTORC1 higher, interfering with the normal turnover of cellular components.

Exercise changed that pattern in the animal models. It activated regulators that lowered DEAF1, bringing mTORC1 activity closer to balance and allowing muscles to clear damaged proteins more effectively while still producing new ones.

Why Responses May Differ

The findings may help explain why physical activity does not affect every aging muscle in exactly the same way. In the study, when DEAF1 levels were extremely high—or when related regulatory proteins were very low—exercise was less able to restore normal repair processes.

That does not make exercise less worthwhile. Instead, it suggests that the condition of a muscle cell before training may influence how strongly it responds.

A Future Research Target

Scientists may eventually investigate whether safely adjusting DEAF1-related pathways can support muscle maintenance in people who cannot be physically active. But that remains a research goal, not a treatment.

For now, the study adds a biological explanation to a familiar observation: regular movement may help muscles not only work harder, but also maintain the internal systems that keep them resilient over time.

References:

1. Sze Mun Choy, Kah Yong Goh, Wen Xing Lee, Weiyi Jiang, Qian Gou, Priya D. Gopal Krishnan, Shi Chee Ong, Kenon Chua, Nathan Harmston, Hong-Wen Tang. Exercise suppresses DEAF1 to normalize mTORC1 activity and reverse muscle aging. Proceedings of the National Academy of Sciences, 2025; 122 (48) DOI: 10.1073/pnas.2508893122