BIONEWS
A Kyushu University team traces the failure to a chemical tag called nitration on hepatocyte growth factor (HGF), the protein that triggers muscle repair; a lab made sulfur compound, lipoic acid trisulfide (LASSS), held the damage down in cells and
Aging muscle doesn't stop repairing because the parts wear out. The signal that triggers repair rusts instead, according to a study from Kyushu University published Friday in Scientific Reports.
The protein in question is hepatocyte growth factor, or HGF. In healthy muscle, HGF sits parked in the connective tissue that surrounds fibers, and it gets released when a fiber is damaged or stretched. Its job is to bind a receptor called c-met on satellite cells, the muscle's resident repair stem cells, and prod them to divide and rebuild what was lost. The Kyushu team, led by Professor Ryuichi Tatsumi, reports that with age, two specific spots on HGF — the tyrosine residues at positions 198 and 250 — pick up a chemical tag called a nitro group. The modification sits in the same patch of the protein that touches c-met, so the modified HGF fits its receptor poorly.
"It's like a rusted key that no longer fits its lock," Tatsumi said in a Kyushu University release describing the work.
Tatsumi's group had previously shown that nitration of HGF rises in aging muscle, but the new paper goes further. The team tested two sulfur-based molecules as protectants: glutathione trisulfide (GSSSG) and lipoic acid trisulfide (LASSS). Both reduced nitration at the Y198 and Y250 sites in the test tube. Neither fully restored HGF's ability to bind c-met at baseline concentrations.
When the ratio climbed past 1-to-4,000 in the test tube, the LASSS-treated protein bound c-met at more than twice the rate of untreated HGF and resisted the disabling effects of nitration. The team calls the resulting complex "Super HGF." The same experiment with GSSSG did not produce the boost, suggesting the effect is specific to LASSS rather than a generic property of trisulfide antioxidants.
In mice whose hindlimbs were unloaded by tail suspension — a standard model of disuse atrophy — pretreatment with LASSS held HGF nitration down compared with untreated controls. GSSSG again showed no measurable benefit. The team frames the result as a candidate strategy for preserving muscle repair during aging, bed rest, and limb unloading, and notes potential cross-species applications including in companion animals.
The c-met binding enhancement has only been shown in biochemical assays. The animal work used young mice with induced disuse, not older animals with age-related decline. No safety, dosing, or efficacy data exist in people, and LASSS is a research compound, not a drug, supplement, or approved therapy. Tatsumi is explicit about the framing: "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."
Independent replication would be the first test, followed by trials in older animals and, eventually, in people. LASSS itself is a lab reagent; a human-usable molecule would still need to be designed.
The mechanistic point stands either way: the team has identified a specific, druggable cause of age-related muscle-repair decline — nitration at two defined sites on a single protein — and shown that chemistry can block it in a dish and in a mouse. That is a thinner result than the wire's "supercharge" framing suggests, but it is also more useful: a defined target, a defined blocker, and a defined next experiment.