This Sulfur Compound Could Be the Key to Aging Muscle Repair

Key takeaways

• A sulfur-based compound called LASSS can more than double the binding strength of hepatocyte growth factor (HGF), a protein central to muscle repair.

• Aging chemically alters HGF through a process called nitration, making it less able to trigger the muscle stem cells that rebuild damaged fibers. LASSS made HGF more resistant to this damage.

• In mice, LASSS reduced HGF nitration and protected muscle-repair signaling during a period of induced inactivity, suggesting the effect holds up beyond an isolated protein in a lab dish.

The repair signal that weakens with age

Skeletal muscle relies on a specific molecular signal to repair itself after strain or injury. That signal starts with hepatocyte growth factor, or HGF, a protein that sits inactive in the structural tissue surrounding muscle fibers until it's needed. When muscle is stressed or damaged, HGF gets released and binds to receptors on satellite cells—the stem cells responsible for muscle maintenance and repair. That binding event is what wakes the stem cells up, prompting them to multiply and rebuild the tissue.

The problem is that this signal doesn't stay reliable forever. Earlier research from the same team found that HGF can undergo a chemical change called nitration, which alters two specific spots on the protein. Once nitrated, HGF struggles to bind its receptor effectively—researchers compare it to a rusted key that no longer fits its lock. That breakdown may be part of why muscle repair becomes less efficient with age, which is what researchers at Kyushu University began to look into.

Searching for a molecule that protects the key

Since the issue isn't a lack of HGF but a loss of its function, the researchers reasoned that a strong antioxidant compound might either prevent the nitration damage or compensate for it. They tested two sulfur-containing molecules known as trisulfides: glutathione trisulfide (GSSSG) and lipoic acid trisulfide, or LASSS.

Both compounds reduced nitration at the vulnerable sites on HGF, but neither fully restored the protein's ability to bind its receptor at typical concentrations. When the researchers increased the concentration of trisulfide relative to HGF, something unexpected happened.

An upgrade, not just a repair

At the higher concentration, HGF mixed with LASSS didn't just get protected—it got enhanced. Its ability to bind to its receptor rose to more than double that of untreated HGF, and it became notably more resistant to nitration damage. GSSSG, the other compound tested, didn't produce this effect.

Lead researcher Ryuichi Tatsumi described this as a genuine surprise: LASSS appears to do more than simply neutralize damaging molecules. It seems to interact directly with HGF, inducing a structural change that creates a more potent version of the protein—something the team is informally calling "Super HGF."

From a test tube to living tissue

To see whether this effect held up outside an isolated protein sample, the researchers tested LASSS in mice experiencing muscle loss from induced inactivity. Mice treated with LASSS beforehand showed significantly less HGF nitration than untreated mice, while GSSSG again failed to provide measurable protection.

That result matters because it moves this discovery from a promising chemistry finding toward something with plausible relevance in living tissue—though the researchers are clear that further studies in aging animals are still needed to establish safety and effectiveness.

The takeaway

Preserving muscle strength as we age is one of the more overlooked aspects of long-term healthy aging, and this research points to a specific, targetable mechanism behind why that repair process slows down—and a compound that may be able to counteract it. It's still early-stage science, with human relevance yet to be established, but the idea of "upgrading" a natural repair protein rather than just replacing it is a compelling direction for future muscle-aging research.

References:

Zushi, K., Seki, M., Mizuochi, R., et al. Enhanced HGF with increased receptor affinity and nitration-dysfunction resistance through interaction with lipoic acid trisulfide. Scientific Reports, 2026; 16(1). DOI: 10.1038/s41598-026-60835-w. ScienceDaily