SALT LAKE CITY — Metformin has been a prescription drug that helps treat diabetes through blood sugar regulation for over a half-century. Now, new research suggests the drug is also capable of preventing muscle atrophy and muscular fibrosis. Study authors at University of Utah Health say metformin’s ability to protect muscles may help the elderly bounce back faster from injury or illness.
More specifically, the research team discovered metformin offers surprising applications on the cellular level. The drug targets “zombie-like cells,” called senescent cells, that are known to impact muscle function. Senescent cells work by secreting factors associated with inflammation that may also underlie fibrotic tissue or a hardening or scarring of tissues. Metformin also appears to reduce muscle atrophy.
“We’re interested in clinical application of this research,” says Micah Drummond, Ph.D., senior author of the study and professor of physical therapy and athletic training at the College of Health, in a media release. “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?”
As all adults grow older, they become more likely to suffer a fall, be hospitalized, or develop chronic disease – and muscle disuse is known to increase these risks. So, the study authors set out to develop a new therapeutic solution capable of correctly targeting muscle recovery and disuse atrophy.
Regardless of age, the human body always has a certain “optimal level” of senescent cells considered beneficial, researchers explain. For younger, healthier people, short-term senescence is necessary for proper injury recovery, and completely blocking the senescent effect would impede the body’s healing efforts. Usually, a younger individual can bounce back more quickly after muscle disuse without intervention like metformin.
“In the case of aging, we know that there’s immune dysfunction,” Prof. Drummond comments. “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 shown in pre-clinical studies. To test the intervention in humans, however, the study authors recruited 20 healthy male and female older individuals for a new multi-week project. Participants underwent a muscle biopsy and MRI before the intervention which involved five days of bed rest. A group of 10 received metformin and the other cohort received placebo pills during a two-week run-in period, followed by each group continuing the placebo or metformin treatment during bed rest.
After the bed rest phase, the group underwent another muscle biopsy and MRI. Then treatments ceased. Finally, all patients completed a seven-day re-ambulation period capped off by a final muscle biopsy.
“We saw two things in our study,” Prof. Drummond adds. “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.”
In an effort to connect these results to senescence, the research team examined muscle biopsies from study participants. This led to the finding that 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,” says lead author Jonathan Petrocelli, Ph.D. Metformin actually helps muscle cells remodel and repair tissues during periods of recovery after inactivity, he explains.
“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.”
Prof. Drummond’s team is now following up on these findings by combining metformin with leucine, an amino acid that promotes growth. The ensuing mixture could accelerate recovery even further. They’ve already demonstrated the potency of the combination in a series of preclinical animal studies.
“Metformin is cheap, effective and quite safe, so it’s exciting to see that we can use it to accelerate recovery for older individuals,” Prof. Drummond concludes.
The study is published in the journal Aging Cell.
