As we grow older, our muscles gradually weaken. Recently, researchers discovered that the hepatocyte growth factor (HGF), a crucial protein for skeletal muscle development, loses its effectiveness due to nitration as we age. The same research team has now created a monoclonal antibody that prevents the nitration of HGF, thus safeguarding its function from age-related decline. This breakthrough was confirmed using muscle cell cultures from rats.
Aging is a universal experience. Even though life expectancy has significantly risen in recent times, we continue to face various health challenges as we grow older. A notable issue is the reduction of muscle mass and function, which can lead to weakness and atrophy. This is especially concerning in aging societies like Japan, where increased longevity can drastically affect quality of life without adequate muscle strength.
Researchers from Kyushu University have made strides toward targeted therapies for age-related muscle atrophy by developing a new antibody that targets the dysfunction of the hepatocyte growth factor (HGF). This protein is vital for muscle growth, repair, and regeneration. Their research has been published in the journal Aging Cell.
Muscle development and repair are supported by a special group of stem cells known as satellite cells. When we exercise or sustain an injury, these satellite cells are activated to create new muscle fibers. A key driver in this process is the HGF.
Professor Ryuichi Tatsumi from the Faculty of Agriculture, who led the study, stated, “Earlier in the year, we discovered that HGF undergoes nitration, which occurs when nitrogen dioxide attaches to the amino acid tyrosine in the protein. This is a common biological modification, but we found that nitration causes HGF to lose its functionality, and this effect intensifies with age.”
Motivated by this discovery, Tatsumi and his team aimed to stop the nitration of HGF. They developed antibodies designed to bind to the protein and prevent nitration from happening.
“Specifically, nitration occurs at the 198th and 250th tyrosine amino acids in HGF. We used rat cell cultures to create and test various antibodies that could specifically target these sites and inhibit nitration,” Tatsumi explained. “After extensive testing, we identified two promising antibodies: 1H41C10 and 1H42F4N. The antibody 1H42F4N effectively blocked the nitration at the 198th tyrosine, while 1H41C10 inhibited nitration at both sites.”
Further testing showed that these new antibodies did not interfere with the activity of HGF itself, indicating that it could still stimulate satellite cells.
The team is enthusiastic about their findings and the significant prospects for new treatments aimed at age-related muscle atrophy and other health issues tied to impaired muscle regeneration.
“Certainly, more research is required before we can apply this in humans, but we are optimistic about the potential we’ve uncovered,” Tatsumi concluded. “HGF has numerous critical roles across various tissues and organs in the body. With continued research, we may discover other therapeutic uses of HGF in different medical conditions.”
