Chris Adams, MD, PhD, Professor of Internal Medicine and Molecular Physiology & Biophysics, has successfully renewed a four-year, $650,000 VA Merit Award. Dr. Adams and his colleagues will use this renewal to continue their investigations of age-related skeletal muscle atrophy, or sarcopenia. Specifically, they will build on the previous grant’s work, which resulted in the discovery that the transcription regulatory protein ATF4 was required for loss of skeletal muscle mass, quality, strength, and exercise endurance capacity during aging. They found that mice lacking ATF4 developed muscle mass and function normally into middle age, but did not exhibit any muscle atrophy when entering old age. Moreover, the team was able to induce atrophy in young mice through forced expression of ATF4. The team also identified an essential ATF4 target gene, p21, as part of their research into the molecular mechanisms behind age-related muscle atrophy.
With this renewal, they will study the mechanisms by which ATF4 activates the p21 gene in muscle fibers; thus far they have isolated seven transcription regulatory proteins that interact with ATF4 in muscle fibers. These proteins represent potential mediators of p21 expression. In addition, they will test whether a targeted reduction of p21 in muscle fibers can prevent or reverse age-related atrophy and whether more information can be discovered about what downstream mechanisms are at work in p21’s effects. As more information on the ATF4/p21 pathway comes to light, potential new therapeutic targets could emerge for treating age-related skeletal muscle atrophy. The benefits of this for an aging population are many when one considers the potential reduction in injury-inducing falls and for increased quality of life. “These studies,” Dr. Adams said, “are a very important step towards our long-term goal of finding a therapy for muscle wasting in elderly veteran patients.”
On Thursday, July 26, Dr. Adams will deliver his presentation “Investigating Mechanisms and Treatment of Skeletal Muscle Atrophy” during Internal Medicine Grand Rounds in the Medical Alumni Auditorium, E331 GH, from noon to 1 p.m.