Lipoic acid trisulfide muscle aging study finds stronger repair signal
Kyushu University researchers say LASSS strengthened HGF, a muscle-repair protein, in lab tests and reduced damage in a mouse atrophy model.
By Priya Raghavan · Science Reporter
3 min read
Kyushu University researchers have identified a possible lipoic acid trisulfide muscle aging pathway that may help preserve the body’s ability to repair skeletal muscle. The team reported in Scientific Reports that the compound, known as LASSS, strengthened a key repair signal and made it more resistant to age-linked chemical damage.
The work focuses on hepatocyte growth factor, or HGF, a protein involved in activating muscle stem cells after injury or mechanical stress. Skeletal muscle often weakens early in aging, with changes that can include scarring, fat buildup inside muscle and loss of fast-twitch fibers needed for quick, forceful movement, according to Kyushu University.
How could lipoic acid trisulfide affect muscle aging?
HGF normally sits in the support structure around muscle fibers until damage or stimulation releases it. It then binds to c-Met receptors on satellite cells, the resident stem cells in skeletal muscle, prompting those cells to leave a resting state and take part in repair.
Kyushu University said the problem in aging muscle may be less about the absence of HGF than about damage to the protein after it is made. In earlier work, the team found that HGF can undergo nitration, a chemical modification at two sites, Y198 and Y250, in the same region HGF uses to connect with c-Met.
That modification reduces HGF’s ability to bind the receptor, weakening the signal that helps muscle regenerate. The researchers describe this as a possible cause of age-related muscle wasting and poorer repair.
What the researchers tested
The team led by Ryuichi Tatsumi, a professor at Kyushu University’s Faculty of Agriculture, tested two sulfur-based antioxidant compounds: glutathione trisulfide, or GSSSG, and lipoic acid trisulfide, or LASSS. Both are trisulfides, a class of molecules with three linked sulfur atoms that has drawn interest for drug development because of its redox chemistry.
In early lab experiments, both compounds reduced nitration of HGF at the Y198 and Y250 sites. When that did not fully restore receptor binding, the researchers increased the molar ratio of HGF to trisulfide from 1:4000 to 1:8000.
At the higher ratio, LASSS produced a stronger effect than expected, according to the study. HGF treated with LASSS bound c-Met more than twice as strongly as untreated HGF and showed greater resistance to nitration-related dysfunction, especially at Y198. GSSSG did not show the same enhancement.
Tatsumi said in the university’s announcement that the result suggests LASSS may do more than neutralize reactive molecules. The compound may interact directly with HGF and cause a small structural change that creates an enhanced form of the protein with stronger receptor binding.
Mouse test shows early protective signal
The researchers also tested LASSS in a mouse model of muscle atrophy caused by tail suspension. Kyushu University said mice pretreated with LASSS had significantly less HGF nitration than untreated mice, while GSSSG again showed no protective effect.
The study does not establish LASSS as a treatment for age-related muscle loss. Kyushu University said more work in aging animals is needed to test effectiveness and safety in living systems.
The researchers said the findings may point toward ways to support muscle repair during aging, long bed rest or other forms of muscle disuse. They also said the HGF mechanism could be relevant not only to humans but also to companion animals such as dogs and cats.
This story draws on original reporting from Medical Xpress.