Japanese Researchers Discover Sulfur Compound That May Slow Age-Related Muscle Loss

Researchers at Kyushu University in Japan have discovered that a synthetic sulfur compound, lipoic acid trisulfide (LASSS), can protect and enhance hepatocyte growth factor (HGF), a key protein responsible for activating muscle-repair stem cells. Aging causes HGF to undergo chemical nitration, preventing it from binding to c-Met receptors. In laboratory tests, LASSS more than doubled HGF's binding affinity, creating a highly active 'Super HGF' form. Pretreatment with LASSS also significantly reduced HGF damage in a mouse model of muscle inactivity, offering a potential future strategy to combat age-related muscle loss in humans and companion animals.

LASSS sulfur compound discovery

• ▪The research team investigated two trisulfide compounds with strong antioxidant properties: glutathione trisulfide (GSSSG) and lipoic acid trisulfide (LASSS).
• ▪Researchers at Kyushu University in Japan discovered that a sulfur-based compound called lipoic acid trisulfide (LASSS) protects and enhances a key muscle-repair protein.
• ▪Lipoic acid trisulfide (LASSS) is a laboratory-created molecule containing three consecutively linked sulfur atoms and is not naturally found in foods or plants.

HGF nitration damage mechanism

• ▪Skeletal muscle decline with age leads to weakness, scarring, fat accumulation within muscle tissue, and a loss of fast-twitch muscle fibers.
• ▪Nitrated hepatocyte growth factor (HGF) loses its ability to bind to c-Met receptors, which impairs the activation of muscle stem cells and contributes to muscle wasting.
• ▪Hepatocyte growth factor (HGF) becomes less functional with age due to a chemical modification process called nitration, where a nitro group attaches to tyrosine sites Y198 and Y250.

Muscle repair satellite cells

• ▪Hepatocyte growth factor (HGF) is released from the supportive network surrounding muscle fibers during injury, mechanical stretching, or exercise.
• ▪Released hepatocyte growth factor (HGF) binds to c-Met receptors on satellite cells, awakening these resident stem cells to divide, develop, and repair damaged muscle fibers.

Laboratory cell culture tests

• ▪Glutathione trisulfide (GSSSG) did not produce the same receptor-binding enhancement for hepatocyte growth factor (HGF) as lipoic acid trisulfide (LASSS) at the 1:8000 molar ratio.
• ▪Hepatocyte growth factor (HGF) treated with lipoic acid trisulfide (LASSS) successfully activated cultured rat muscle satellite cells, even at doses below the normal optimal range.
• ▪In laboratory experiments, mixing hepatocyte growth factor (HGF) with lipoic acid trisulfide (LASSS) at a 1:8000 molar ratio more than doubled HGF's binding affinity to c-Met.

Mouse hindlimb suspension study

• ▪Mice pretreated with lipoic acid trisulfide (LASSS) in drinking water for three days before a five-day tail suspension period showed significantly reduced nitration of HGF at Y198.
• ▪Glutathione trisulfide (GSSSG) did not produce a clear protective effect against hepatocyte growth factor (HGF) nitration in the suspended mouse model.
• ▪The mouse study utilized three or four young male mice per group and did not test whether lipoic acid trisulfide (LASSS) preserved muscle strength, size, or regeneration.

Age-related muscle loss research

• ▪Further studies in aging animals and human clinical trials are required to confirm the safety, effectiveness, and long-term safety of lipoic acid trisulfide (LASSS).
• ▪Researchers believe the therapeutic effects of lipoic acid trisulfide (LASSS) on muscle repair could apply broadly to both humans and companion animals like cats and dogs.