Diabetes drug that regulates blood sugar can also prevent muscle atrophy and muscular fibrosis – which can help the elderly bounce back faster from injury or illness.
University of Utah Health researchers have discovered that metformin, a common drug used in diabetes treatment for more than half a century, has surprising applications on a cellular level. It can target “zombie-like cells,” called senescent cells, which impact muscle function. Senescent cells secrete factors associated with inflammation that may underlie fibrotic tissue, a hardening or scarring of tissues. Metformin also reduces muscle atrophy.
“We’re interested in clinical application of this research,” said Prof Micah Drummond, senior author of the study and professor of physical therapy and athletic training at the College of Health. “For example, knee surgeries in the elderly are notoriously hard to recover from. If we give a metformin-type agent during the recovery period, could we help the muscles get back to normal faster?”
Reinvigorating muscle recovery
As adults age, they’re more likely to fall, be hospitalised, or develop chronic disease, and muscle disuse increases these risks. The research team wanted to find a therapeutic solution that could properly target both disuse atrophy and muscle recovery.
There’s an optimal level of senescent cells that are beneficial, no matter your age. In younger, healthier people, short-term senescence is required for a proper recovery from injury, and completely blocking the senescent effect impedes the body’s efforts to heal. Typically, a younger person can bounce back more easily after muscle disuse without the use of an intervention such as metformin.
“In the case of aging, we know that there’s immune dysfunction,” said Drummond. “As you get older, it becomes harder for your body to clear senescent cells and they accumulate. That’s one reason recovery is much slower for the elderly after periods of disuse.”
Metformin’s anti-senescent properties have been demonstrated through pre-clinical studies. “When participants took metformin during a bed rest, they had less muscle atrophy. During the recovery period, their muscles also had less fibrosis or excessive collagen. That build-up can make it harder for the muscle to properly function,” Prof Drummond said.
Tying these results to senescence, the research team examined muscle biopsies from study participants. They found that the participants who took metformin had fewer markers of cellular senescence.
“This is the first paper that has made the direct connection between a therapy targeting cellular senescence and improved muscle recovery following disuse in aging,” said lead author Prof Jonathan Petrocelli. He explained that metformin helps muscle cells better remodel and repair tissue during periods of recovery after inactivity.
“Our real goal is to have patients maintain their muscle mass and function as they age, because atrophy and weakness are some of the strongest predictors of disease development and death,” he said.
