Exercise to Improve Age-Related Loss of Function and Corresponding Alterations in Gene Expression

Abstract

The “gray wave,” the increasing population aged 65 and older, will double over the course of the next 30 years. This is a concern as it results in an increased prevalence of age-associated diseases such as diabetes, cardiovascular disease, frailty (inability of the body to maintain homeostasis), and sarcopenia (age-related loss of muscle mass and strength). Frailty and sarcopenia add to the progressive loss of functional ability and independence among older adults, resulting in a lower quality of life. Exercise can reduce the risk of these diseases, but it is not a cure nor is it physically feasible for every individual4. Therefore, it is essential to investigate the latent molecular mechanisms of aging and exercise to develop future therapeutic targets. Previously, we discovered that as aging occurs, calcium handling in skeletal muscle is changed. The sarcoplasmic reticulum calcium transport ATPase (SERCA), a pump that transports calcium to the lumen of the sarcoplasmic reticulum, stimulates relaxation of the muscle. Sarcolipin (SLN), an uncoupler of the SERCA pump, decreases the reaction rate of calcium reuptake by preventing the pumping of calcium into the lumen without negatively regulating ATP hydrolysis12. After monitoring four months of endurance training (two modes: voluntary wheel running, n=8 per groups; high-intensity interval training, n=10 per group) in adult (10-month-old) and older (26-month-old) mice, we attempted to establish the skeletal muscle gene expression of SLN along with the similarly functioning proteins, myoregulin and phospholamban. Using gastrocnemius muscle, we isolated RNA, measured mRNA expressing with q-rt-PCR, and determined SLN content with Western Immunoblotting. We hypothesized that increased levels of SLN contribute to age-associated muscle dysfunction, but that endurance training might restore muscle health in older mice by lessening SLN expression. We conclude that, compared to controls, significant improvement was observed in the physical function and body composition of both exercise groups.