Healthy, robust muscles are required for movement and normal bodily functions, but muscles can decline significantly as we age. This can increase the risk of physical problems, falls, and breaks that can lead to other health issues; may make wounds harder to repair; and can increase the burden on caregivers. But exercise can help boost self-repair in muscles that are aging, according to new research reported in the Proceedings of the National Academy of Sciences (PNAS). These findings may help explain why physical activity is among the most effective habits to maintain mobility and physical strength as people get older.
There is an important biochemical pathway in muscles that relies on a molecule known as mTORC1. This growth pathway helps control protein production and the maintenance of muscles, but it can also become too active as people get older. During aging, new proteins that build muscle are generated because of this pathway, but the removal of aberrant proteins slows down, and the damaged proteins begin to accumulate. This imbalance can put stress on muscles and cause them to weaken over time.
This study has shown that the activity of a gene known as DEAF1 increases in aging muscles, which overactivates mTORC1. The protein pathway is disrupted by this overactivity; proteins are not removed when damaged, and muscle cells begin to degrade.
Usually, DEAF1 activity is under the control of regulatory molecules known as FOXOs, but FOXO function is also impaired during aging. The decline of FOXO function allows DEAF1 levels to increase, and balance is lost in muscle cells.
However, exercise helps maintain and even reverse the loss of this crucial balance, but only while the system can still respond.
"Physical activity activates certain proteins which lower DEAF1 levels, bringing the growth pathway back into balance. This allows aging muscles to clear out damaged proteins, rebuild themselves properly, and help them stay stronger and more resilient,” said senior study author Tang Hong-Wen, an Assistant Professor at Duke-NUS Medical School.
In some older muscles, DEAF1 levels may stay high, or FOXO can be too damaged to trigger the rejuvenation that exercise can stimulate. Therefore, not all older adults will see all of the benefits that exercise may provide. This emphasizes that existing muscle physiology can have a significant influence on the efficacy of any potential interventions.
Although these findings used fruit fly and aging mice as models, they may apply to humans since the underlying molecular mechanisms are often similar in muscles. Rising DEAF1 levels caused muscles to rapidly weaken, but decreasing DEAF1 levels restored proper protein levels and muscle strength in both models.
This data may also provide new insights into how to help people recover from chronic diseases, illnesses, or surgery. It may be possible to manipulate the levels of DEAF1 to provide some of the benefits of exercise, without requiring the physical activity.
"This study helps explain at a molecular level why aging muscles lose their ability to repair themselves and why exercise can restore that balance in some individuals. By identifying DEAF1 as a key regulator in this process, these findings may lead to new ways in which the benefits of exercise can be brought to societies with rapidly aging populations,” added Professor Patrick Tan, Senior Vice-Dean for Research at Duke-NUS.
Sources: Duke-NUS Medical School, Proceedings of the National Academy of Sciences (PNAS)
