Losing muscle in old age is not necessarily a shortage of building material. Findings from a group in Fukuoka locate the problem elsewhere: the signal that triggers repair in the first place is chemically disabled. And that signal, it seems, can be protected.
At the centre of the work is hepatocyte growth factor, or HGF. It sits inactive in the supportive tissue between muscle fibres. When a muscle is loaded or injured, HGF is released and binds to the c-met receptor on satellite cells, the resident stem cells of skeletal muscle. Only that contact rouses the cells from their resting state: they multiply, mature and rebuild damaged fibres.
With age, the contact is lost. A nitro group attaches to the amino acids Y198 and Y250 — precisely the region HGF uses to dock with the receptor. The growth factor is still present, but the key no longer fits the lock. The consequences are familiar: tissue regenerates poorly, loses strength, scars, accumulates fat and sheds the fast-twitch fibres needed for powerful movement. For older people that means a higher risk of falls and fractures, and often the loss of independence.
HGF becomes "Super HGF"
The team led by Ryuichi Tatsumi at Kyushu University's Faculty of Agriculture therefore turned to antioxidants with unusual sulfur chemistry: glutathione trisulfide (GSSSG) and lipoic acid trisulfide (LASSS), molecules carrying three directly linked sulfur atoms. Both suppressed nitration at Y198 and Y250 in the experiments — yet neither fully restored the ability to bind.
The breakthrough came when the researchers raised the ratio of HGF to trisulfide from 1:4000 to 1:8000. Binding to c-met was then more than twice as strong as with untreated HGF, and the growth factor resisted nitration far better, especially at Y198. This held for LASSS alone; GSSSG produced no such effect. Tatsumi suspects the compound does more than mop up reactive molecules: it may slightly alter the structure of HGF itself, creating an enhanced form the team calls "Super HGF". "This exceeded our expectations," he says.
The finding survived a move into living tissue. In mice whose muscles were wasting from enforced inactivity, nitration was markedly lower after pretreatment with LASSS than in untreated animals. GSSSG again did nothing.
An application remains distant. The study, published on 24 July 2026 in "Scientific Reports", offers laboratory results and a single mouse model; efficacy and safety still have to be demonstrated in ageing animals. What is striking is the direction of travel: not adding more growth factor, but keeping the existing supply functional — in age-related muscle loss as much as after long periods of bed rest. The authors expect the mechanism to apply broadly, down to companion animals such as cats and dogs.