The mouse study suggests certain compounds can prevent nitration of hepatocyte growth factor (HGF), preserving its ability to activate muscle satellite cells that drive repair. In vitro, two protective compounds reduced HGF nitration; lipoic acid trisulfide (LASSS) also enhanced HGF receptor binding at higher doses. Oral LASSS lowered HGF nitration in young mice after five days of hindlimb disuse, but the study did not test aged animals or measure muscle recovery. Further research is needed to assess long-term benefits, safety, and relevance to humans.
Compounds May Shield Muscle-Repair Protein From Age-Related Damage — Mouse Study Highlights LASSS
A new study shows that several compounds can help prevent a chemical reaction that hinders muscle regrowth. | Credit: ROGER HARRIS/SCIENCE PHOTO LIBRARY via Getty Images
Scientists report evidence from a new mouse study that certain compounds can prevent a chemical modification that weakens a protein central to muscle repair, potentially helping preserve muscle function with age.
The study, published July 24 in Scientific Reports, focuses on satellite cells — the stem cells that sit beside skeletal muscle fibers and activate to repair damage from everyday use. Activation depends on a signal molecule called hepatocyte growth factor (HGF). Researchers found that HGF can be chemically altered by nitration, caused by the reactive molecule peroxynitrite, which reduces HGF's ability to bind its receptor and activate satellite cells.
What the Researchers Did
Building on previous work showing increased HGF nitration in older animals, the team tested two protective compounds that can intercept highly reactive chemicals and shield proteins from oxidative damage. In lab assays, treating purified HGF with either compound before exposing it to peroxynitrite markedly reduced nitration and preserved HGF's ability to activate satellite cells cultured in vitro.
Regular physical activity can help older adults preserve muscle, but even so, muscular tissue tends to weaken with age. | Credit: Maskot via Getty Images
One compound in particular — lipoic acid trisulfide (LASSS) — produced especially strong effects. At higher concentrations LASSS not only blocked nitration but also increased HGF's receptor binding in vitro, suggesting it might chemically modify HGF to enhance signaling.
Translation to Living Animals
To test in vivo relevance, researchers gave young mice LASSS in drinking water while the animals experienced five days of hindlimb unloading, a short-term model of muscle disuse known to raise HGF nitration. LASSS-treated mice showed substantially lower HGF nitration around muscle cells than untreated controls. "It's pretty remarkable" that oral LASSS produced a measurable change, said Matthew Krause, a muscle physiologist not involved in the study.
Ryuichi Tatsumi, co-author and muscle physiologist at Kyushu University, noted that peroxynitrite forms when unstable nitrogen and oxygen radicals react — a process that becomes more common with age and can damage proteins like HGF.
Limitations and Next Steps
The authors emphasize important caveats: the experiments used young mice and short-term disuse; the team did not measure muscle mass, strength, or recovery, nor did they test LASSS in aged animals. Longer studies in older animals are needed to determine whether reducing HGF nitration translates into better muscle regeneration, improved strength or preserved mobility. Safety, dosing, and efficacy in humans remain untested.
Beyond muscle biology, protein nitration is implicated in other age-related conditions — for example, nitrated proteins accumulate in Alzheimer’s disease — so strategies to prevent nitration could have broader therapeutic potential. The researchers express cautious optimism that further work could lead to treatments that protect proteins and tissue function during aging.
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