Exercise Lowers Gene DEAF1 to Restore Aging Muscle in Animals

The work was published in the Proceedings of the National Academy of Sciences of the United States of America in 2025. The team used fruit flies and cultured mouse muscle cells called C2C12 myotubes. The full text we reviewed did not give the number of flies per experiment. The study and the press coverage describe the findings as applying to animals, not people.

The gene is called DEAF1. Muscle needs a balance between making new proteins and clearing out damaged ones. A cell-growth pathway called mTORC1 helps run that balance. In aging muscle, the authors write, mTORC1 becomes overactive. That is linked to sarcopenia, the loss of muscle mass and function with age. What drives the overactivity was unclear.

The researchers report that DEAF1 is one driver. According to the study, DEAF1 binds the promoter of the mTOR gene and raises its activity. In the mouse muscle cells, they found 16,611 DEAF1 binding sites, about 75% at gene promoters. More DEAF1 meant more mTOR messenger RNA. Less DEAF1 meant less.

In flies, muscle strength was tracked by climbing ability at weeks 1, 3 and 6. Climbing declined by week 6. Lowering Deaf1 in muscle significantly preserved muscle function. Raising it had no effect early on but worsened defects at week 6.

Aged fly muscle showed more protein production, less clearing of damaged proteins, more protein clumps and more markers of cell senescence, a state in which cells stop dividing and can harm nearby tissue. Lowering Deaf1 reduced these changes. Raising it intensified them. The mTORC1-blocking drugs rapamycin and everolimus suppressed Deaf1-induced muscle defects in flies. This supports the idea that mTORC1 sits downstream of DEAF1. In the mouse cells, the same pattern held. These were experiments in animals and cells; nobody should start, stop or change any medication, treatment or exercise regimen without consulting their clinician.

Exercise enters through a family of proteins called FOXO. The study states that exercise suppresses Deaf1 by activating FOXO. That restores mTORC1 balance and eases muscle aging. When FOXO was inhibited, or Deaf1 was overexpressed, the benefits of exercise were blocked. This is the strongest evidence in the paper that the pathway is needed for exercise to work in these models.

Here is what it may mean for health, with caution. The study did not test when exercise should begin, and it did not study people. The press release from Duke-NUS Medical School, which led the work, says exercise may no longer fully restore muscle repair when DEAF1 is extremely high or FOXO activity is very low, and that the benefits may diminish when the system becomes too disrupted. The release also states that the findings do not suggest exercise loses its value with age. Whether any of this applies to people is untested, and this is where the argument is weakest: it rests on animal and cell work and says nothing about timing.

The release quotes lead author Tang Hong-Wen: "Exercise can reverse this process, correcting the imbalance." The study's own language is similarly strong: its title says exercise will reverse muscle aging, and the text says the pathway rejuvenates aging muscle. Its closing caution is that targeting the FOXO-DEAF1-mTORC1 axis may offer therapeutic potential.

One caveat on dates. The release is dated Oct. 15, 2026, but the paper is from 2025. Coverage of the mouse experiments comes from the release, since the portion of the paper we reviewed centered on flies and mouse muscle cells.

What to watch next

Whether DEAF1 levels and FOXO activity can be measured in human muscle, and whether studies in older adults show that they predict who benefits most from exercise.

Faulty Myelin-Making Brain Cells Linked to Faster Cognitive Decline After 70 Sleep Scientists Say Permanent Standard Time Better Fits the Body Clock Exercise Lowers Gene DEAF1 to Restore Aging Muscle in Animals Overlooked Peptide P3 May Help Drive Alzheimer's, UC Santa Cruz Chemist Argues