Common glucose-lowering drug may also work to prevent muscle atrophy in older adults

For older people, administering metformin before or during a period of reduced physical activity appears to have potential benefits for the muscles, such as reducing atrophy and improving recovery, as reported by a team of US-based researchers.

In a multi-week study where 20 healthy older adults had to undergo 5 days of bed rest, those who received metformin (n=10) during a 2-week run-in period were found to have less muscle atrophy during the bed rest compared with those who received placebo (n=10).

MRI images showed that the mean total myofiber cross-sectional area after the 2-week run-in period, 5 days of bed rest, or 7 days of recovery did not differ between the metformin- and placebo-treated groups. However, the metformin-treated group had fewer smaller (>3,000 to <4,000 μm²) and greater larger (>5,000 to <6,000 μm²) myosin heavy chain (MyHC) I fibers after the run-in period and the bed rest. [Aging Cell 2023;doi:10.1111/acel.13936]

“During the recovery period, [the] muscles [of the metformin-treated participants] also had less fibrosis or excessive collagen,” the build-up of which can make it harder for the muscle to properly function, according to senior author of the study Dr Micah Drummond from the University of Utah Health in Salt Lake City, Utah, US.

The findings were complemented by muscle biopsy reports, which indicated that the metformin-treated group had fewer markers of cellular senescence than the placebo-treated group.

Antisenescent properties

A commonly prescribed glucose-lowering drug in individuals with type 2 diabetes mellitus, metformin has the potential to improve muscle regeneration following burn injury and reduce muscle atrophy in immobilized mice, as well as to improve collagen remodelling and partially restore myofiber cross-sectional area during re-ambulation following hindlimb unloading in aged mice. [Cell Metab 2020;32:15-30; Connect Tissue Res 2023;64:26-39; Stem Cell Res Ther 2020;11:18; FASEB J 2021;35:e21862]

Metformin has been also shown to prevent cellular senescence and block the senescence-associated secretory phenotype (SASP). [Shock 2023;59:646-656; Aging Cell 2018;17:e12765; Mech Ageing Dev 2013;134:548-559; Aging Cell 2013;12:489-498]

“In the case of aging, we know that there’s immune dysfunction,” Drummond stated. “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 [muscle] disuse.”

In light of the present data, Drummond and colleagues believe that metformin treatment 2 weeks before and during muscle disuse could improve older adult myofiber remodelling during early re-ambulation through alterations in collagen deposition. The effects of metformin on collagen deposition, according to the researchers, may be related to increased anti-inflammatory transcriptional programs and reduced whole muscle and muscle resident fibro-adipogenic progenitor senescence/SASP.

“We’re interested in clinical application of this research,” Drummond said. “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?”

Drummond and colleagues shared that they are now looking at whether combining metformin with leucine, an amino acid that promotes growth, could accelerate recovery even further.

“Metformin is cheap, effective and quite safe, so it’s exciting to see that we can use it to accelerate recovery for older individuals,” Drummond added.