Working out doesn’t just build muscle but, in later life, helps maintain a powerful cellular machine that repairs damaged tissue with efficiency. Scientists have now not only discovered how this system works but found a way to keep it balanced in older muscles.
Duke-NUS Medical School researchers, along with scientists from Singapore General Hospital and Cardiff University, have discovered the cellular mechanism within muscles that helps people retain mobility and strength later in life – and it comes through working out.
We all know that from midlife, muscle function begins to deteriorate and we have to work harder to maintain the tissue or face increasing risk of falls, slower injury recovery and poorer blood sugar regulation. Now, researchers have found that the key to maintaining muscle function is a growth pathway known as mTORC1, which oversees protein production and tissue health. The delicate balance of this pathway is thrown off as we age, adding new protein without removing damaged molecules in the process. And these rubbish proteins contribute to the loss of strength in the tissue.
In this study, the team identified the transcription factor DEAF1, a gene which drives this dysregulation in aging muscles, switching on overactivity in the mTORC1 system and disrupting the protein exchange that functions normally in younger tissue. The gene’s activity is managed by regulatory proteins known as FOXOs – which, unsurprisingly, lose the ability to properly keep the gene in check, as we get older. So instead of a smoothly operating system that repairs and strengthens tissue, it actually ends up accelerating muscle loss.
Duke-NUS Medical School
So where does working out come into this? Well, exercise can actually reverse this process to enable efficient muscle repair – as long as the system’s cellular puzzle pieces remain responsive.
“Exercise can reverse this process, correcting the imbalance,” said Tang Hong-Wen, an associate professor at Duke-NUS. “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.”
When DEAF1 levels are too high or the activity of FOXO proteins are muted, exercise alone may not be enough to restore muscle power. The researchers believe this could explain why physical activity can benefit some older adults more than others.
“Exercise tells muscles to ‘clean up and reset,'” said lead author Priscillia Choy Sze Mun, a research assistant with the Cancer and Stem Cell Biology Programme at Duke-NUS. “Lowering DEAF1 helps older muscles regain strength and balance, almost like hitting the rewind button. With millions of older adults at risk of muscle decline, understanding DEAF1 could lead to new ways to protect muscles and improve quality of life.”
The team made its discoveries using older mice and fruit flies, and in both models the scientists saw the same pattern emerge: Boosting DEAF1 levels resulted in increased muscle weakness, and muting activity restored the system’s balance and in turn promoted muscle repair and strength. While these experiments were on simpler models than humans, the process remained the same across the very different species, suggesting that our tissue is likely subjected to the same pathway and age-related dysregulation.
DEAF1 is already known to influence stem cells in muscles, which are important in tissue repair and regrowth. These stem cells decline with age, too. However, manipulating DEAF1 levels could be a way to ensure the cellular benefits of exercise are maintained well into our senior years, even without a whole lot of 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,” said Patrick Tan, a professor at Duke-NUS. “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.”
The study was published in the journal PNAS.
Source: Duke-NUS Medical School
