Developing a treatment for age-related muscle atrophy

With increased age comes decreased muscle function — but a new study has found a potential therapy to help avoid muscle atrophy.

Decrease of muscle mass and function, leading to weakness and atrophy, is a pressing concern in a rapidly aging society. When people are living longer without proper muscle strength, quality of life can be drastically diminished.

In findings that may eventually lead to targeted therapies that treat age-related muscle atrophy, a group of researchers from Kyushu University have developed a new antibody that targets and prevents the dysfunction of the protein hepatocyte growth factor or HGF: a critical factor in skeletal muscle development, regeneration and repair. Their findings were published in the journal Aging Cell.

The process of building new muscle

Muscle growth and regeneration occurs due to a population of stem cells called satellite cells. When a person trains their muscles, or becomes injured, these satellite cells are activated to form new muscle fibres. One of the key activators that tells satellite cells to build new muscle is HGF.

“Earlier this year, our team found out that HGF undergoes a process called nitration. This is when a molecule of nitrogen dioxide attaches to the amino acid tyrosine on the protein,” said Professor Ryuichi Tatsumi of the Faculty of Agriculture, who led the study.

“This is a common modification we see in biology. However, we found that HGF loses its physiological activity when it becomes nitrated, and this phenomenon accumulates with age.”

Based on this, Tatsumi and his team wanted to find a way to block nitration on the HGF protein. One of the most effective ways of doing this is to develop antibodies that bind to the protein and block it from being nitrated in the first place.

“To be specific, nitration happens on the 198th and 250th tyrosine amino acid on HGF. So, using rat cell cultures, we developed and screened a series of antibodies that would specifically bind to these areas and block nitration,” he said.

“After a series of tests, we found two candidate antibodies: 1H41C10 and 1H42F4N. Antibody 1H42F4N blocked nitration of the 198th tyrosine. Surprisingly, 1H41C10 blocked both tyrosine sites.”

Through further testing the team found that the new antibodies did not disrupt HGF activity itself, meaning it could still activate satellite cells.

Looking to the future

The research team believes their findings have significant potential in terms of developing new treatments for age-related muscle atrophy, along with other health conditions related to impaired muscle regeneration.

“Of course, further work is needed before we see a use case in humans, but we are encouraged by the great potential our work has uncovered,” Tatsumi said. “HGF has numerous important functions in a variety of tissues and organs throughout the body. With further research we may be able to find other therapeutic applications of HGF in other pathologies.”

Image credit: iStock.com/Jacob Wackerhausen