When contemplating muscle function, diabetes might not be the foremost consideration. Surprisingly, a commonly prescribed diabetes medication, Metformin, known for its role in regulating blood sugar levels, has demonstrated the ability to combat muscle atrophy and muscular fibrosis. This newfound application of Metformin, uncovered by researchers from the University of Utah Health, operates on a cellular level by targeting senescent cells, often referred to as “zombie-like cells,” which negatively affect muscle function. Senescent cells release inflammatory factors that may contribute to the development of fibrotic tissue, a condition characterized by tissue hardening or scarring. Additionally, Metformin has been found to mitigate muscle atrophy. The research findings were recently published in the journal Aging Cell.
Micah Drummond, Ph.D., the senior author of the study and a professor of physical therapy and athletic training at the College of Health, expressed their interest in the practical application of this research. For instance, they pondered whether administering a Metformin-like agent during the recovery period after knee surgeries in the elderly could expedite muscle restoration and help them regain normal muscle function more rapidly.
As individuals age, they become more susceptible to falls, hospitalization, and chronic illnesses, with muscle disuse exacerbating these risks. The research team aimed to identify a therapeutic solution capable of addressing both disuse-induced muscle atrophy and muscle recovery.
It’s worth noting that there exists an optimal level of senescent cells that offer benefits regardless of one’s age. In younger and healthier individuals, brief senescence periods are necessary for proper injury recovery. Completely blocking the senescent effect can impede the body’s natural healing processes. Typically, younger individuals can recover more effectively from muscle disuse without interventions like Metformin.
Drummond emphasized the role of immune dysfunction in aging, explaining that as individuals grow older, their bodies struggle to clear senescent cells, leading to their accumulation. This accumulation is one reason why recovery is notably slower in the elderly after periods of muscle disuse.
Metformin’s ability to combat senescence has been demonstrated in preclinical studies. To assess the intervention’s effectiveness in humans, the research team enrolled 20 healthy older adults (both male and female) in a multi-week study. The participants underwent muscle biopsies and MRI scans before a five-day bed rest period. During a two-week run-in phase, one group received Metformin, while the other received placebo pills. Both groups continued their respective treatments during the bed rest period. After bed rest, participants underwent additional muscle biopsies and MRI scans, followed by cessation of treatments. Subsequently, all participants completed a seven-day re-ambulation period, concluding with a final muscle biopsy.
The study yielded two significant findings. Firstly, individuals who took Metformin during bed rest experienced less muscle atrophy. Secondly, during the recovery phase, their muscles exhibited reduced fibrosis, characterized by decreased collagen buildup, which can hinder proper muscle function. Connecting these results to senescence, the research team analyzed muscle biopsies and found that participants who took Metformin displayed fewer markers of cellular senescence.
Jonathan Petrocelli, Ph.D., the lead author of the study, highlighted the direct connection between a therapy targeting cellular senescence and enhanced muscle recovery following periods of inactivity in aging individuals. He emphasized that Metformin facilitates more effective remodeling and repair of muscle tissue during recovery after periods of inactivity.
Drummond’s team is now exploring the combination of Metformin with leucine, an amino acid that promotes growth and could potentially further accelerate recovery. They have already demonstrated the potency of this combination in preclinical animal studies.
In conclusion, Metformin, known for its affordability, effectiveness, and safety, shows promise in accelerating the recovery of older individuals, thereby helping them maintain muscle mass and function as they age. Atrophy and weakness, which are strongly linked to disease development and mortality, could potentially be mitigated through such interventions. The study was funded by the National Institute on Aging.