Metformin may prevent muscle loss from disuse atrophy by effects on senescent cells

Abstract

Muscle loss and sarcopenia is increasingly prevalent especially in the ageing population and is a recognized independent factor for increased risks of morbidity and mortality. Previous evidence have shown that diabetes accelerates sarcopenia. This is relevant since diabetes has increasingly become one of the most important problems affecting the elderly, leading to increased risks of weakness, frailty, and adverse health outcomes. Strategies to understand the mechanisms of and the prevention of muscle loss is therefore important. Furthermore, developing a therapeutic solution that could properly target both disuse atrophy and muscle recovery may improve health outcomes following surgery or period of inactivity.

A recent study published in the journal Aging Cell [1] by researchers from the University of Utah have shown that Metformin, has surprising applications on a cellular level to target muscle loss. It works by targeting so called senescent cells, which impact muscle function. Senescent cells secrete factors associated with inflammation that may underlie muscle fibrosis. In younger, healthier people, short-term senescence is important for recovery from injury, and completely blocking the senescent effect impedes the body's efforts to heal. Conversely in the ageing, immune dysfunction results in reduced clearance of senescent cells and hence a slower recovery for the elderly after periods of disuse. Metformin's anti-senescent properties have previously been demonstrated through pre-clinical studies. To test the intervention in humans in the present study, the researchers randomized 20 individuals to receive metformin (N = 10) or placebo (N = 10) and participants undergo a muscle biopsy and MRI before and after the intervention, which involved 5 days of bed rest. All patients then completed a seven-day re-ambulation period followed by a final muscle biopsy.

The study showed that participants who took Metformin during a bed rest had less muscle atrophy and during the recovery period, their muscles also had less fibrosis or excessive collagen. Participants who took Metformin had fewer markers of cellular senescence which may explain the mechanism of the observed effects. Further studies are ongoing to incorporate the anti-senescence effects of metformin with leucine, an amino acid that promotes growth and could accelerate recovery even further. Evidence based from these experimental studies may form the basis for wider clinical studies to investigate the efficacy of metformin to prevent muscle loss and frailty as a result of disuse atrophy.