Researchers at Duke-NUS investigated how a protein-control system tied to muscle maintenance changes with age and how exercise counters that decline. The study shows that mTORC1, a cellular complex that normally builds and repairs muscle, can become chronically overactive during aging. The team identifies a gene regulator, DEAF1, as a key driver that increases protein synthesis in muscle cells while blocking the clearance of damaged proteins. This imbalance can damage muscle cells and contribute to sarcopenia, the progressive loss of muscle mass and function linked to age.
To test the effect of activity, aging mice performed endurance workouts that included an exhausting treadmill run, while a control group remained sedentary. After exercise, the active mice had marked reductions in mTORC1 activity compared with sedentary animals. Further analysis revealed that exercise lowers DEAF1 through activation of a set of longevity-related genes called FOXO; when FOXO is activated it suppresses DEAF1 and helps mTORC1 return toward normal activity, which may protect muscle cells.
The senior author is Hong-Wen Tang, with co-lead authors Sze Mun Choy, Kah Yong Goh, and Wen Xing Lee. The work appears in the Proceedings of the National Academy of Sciences and highlights a FOXO–DEAF1–mTORC1 pathway linking age, muscle decline, and physical activity. The authors note that drugs targeting DEAF1 or boosting FOXO could mimic some benefits of exercise and help prevent age-related muscle weakening. Funding came from the Singapore Ministry of Education; Diana Koh Innovative Cancer Research Award; National Academy of Medicine; and National Medical Research Council. Source: Duke University.
Difficult words
- sarcopenia — age-related loss of muscle mass and function
- chronically — in a way that continues for a long time
- overactive — more active than normal in harmful way
- regulator — a person or thing that controls a process
- clearance — removal of unwanted or damaged material
- sedentary — not physically active; spending much time sitting
- pathway — a series of connected actions or processes
- suppress — stop or reduce an action or activitysuppresses
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Discussion questions
- Why might lowering DEAF1 protect muscle cells during aging? Use reasons from the article.
- What are possible benefits and risks of drugs that boost FOXO instead of exercise, based on the study's claims?
- How could the finding about exercise reducing mTORC1 activity change advice for older adults' physical activity?
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