A muscle repair protein may have got an unexpected boost.
Researchers led by Professor Ryuichi Tatsumi of Kyushu University’s Faculty of Agriculture say a sulfur-based compound called lipoic acid trisulfide, or LASSS, appears to protect and enhance hepatocyte growth factor, or HGF, a protein involved in repairing skeletal muscle. The results were published on July 24, 2026, in Scientific Reports.
Skeletal muscle often starts to deteriorate relatively early in aging. Over time, that can lead to loss of strength, increased scarring, fat buildup in muscle tissue and a decline in fast twitch fibers that support rapid, powerful movements.
The study focused on HGF, which helps start skeletal muscle repair. Under normal conditions, HGF stays inactive within the structural network around muscle fibers. When muscle tissue is injured or mechanically stimulated, HGF is released and attaches to c-met receptors on satellite cells, the stem cells that maintain and repair skeletal muscle.
That signal brings satellite cells out of their inactive state, allowing them to multiply, mature and help rebuild damaged muscle fibers.
The team said aging can disrupt that repair system. Previous research from the group found HGF can undergo nitration, a chemical modification that adds a nitro group at two sites on the protein, Y198 and Y250. Those sites sit in the same region HGF uses to connect with c-met, and after nitration, HGF can no longer attach effectively to the receptor.
“HGF is not necessarily missing as we age,” Tatsumi said. “Rather, it can be chemically altered after it is made. That led us to wonder whether a compound with strong antioxidant capacity might protect HGF, either by preventing nitration or by compensating for the functional loss it causes.”
The researchers tested two antioxidant compounds, glutathione trisulfide, or GSSSG, and LASSS. Early experiments showed both reduced nitration at the Y198 and Y250 sites on HGF, but neither fully restored the protein’s ability to bind to its receptor.
The researchers then increased the molar ratio of HGF to trisulfide from 1:4000 to 1:8000.
At the higher concentration, HGF mixed with LASSS bound to c-met at more than twice the level of untreated HGF, according to the researchers. The protein also became more resistant to the loss of function caused by nitration, particularly at Y198. The team said GSSSG did not produce the same effect.
“This exceeded our expectations,” Tatsumi said. “We knew trisulfides had diverse biological functions, but we never expected that simply mixing HGF with LASSS would produce such a striking effect.
“What this tells us is that LASSS does more than simply neutralize reactive molecules. It may interact directly with HGF and induce a subtle structural change, creating an enhanced ‘Super HGF’ form that binds c-met more strongly and resists nitration.”
The findings suggest LASSS may directly alter the structure of HGF in a beneficial way, creating a more active form of the protein that connects more strongly with its receptor while resisting chemical damage.
The team also tested LASSS in mice with muscle atrophy caused by tail suspension. Mice treated with LASSS before the procedure had significantly lower levels of nitration than untreated mice. The researchers said GSSSG did not provide measurable protection.
The results suggest the effects of LASSS were not limited to experiments involving isolated proteins. The researchers said more studies in aging animals are still needed to determine if LASSS is safe and effective in vivo.
The paper is titled Enhanced HGF with increased receptor affinity and nitration-dysfunction resistance through interaction with lipoic acid trisulfide.
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