Potential For Treatment Of Age-Related Muscle Atrophy By Exogenous Nitric Oxide And Exercise

In adult muscle, activation of satellite cells (SCs) is required for muscle maintenance, growth and repair. SCs are activated in response to exercise, stretch, trauma, denervation and nitric oxide (NO). The muscle response to exercise is age-dependant and muscle-specific and may be a factor in age-related muscle atrophy. The purpose of this experiment was to determine the effects of treatment with an NO-donor isosorbide dinitrate (ISDN) and exercise on muscle mass, SC activation (DNA synthesis), NOS-I and β-dystroglycan and fiber cross-sectional area (CSA) on muscle in 18-month-old mice. Mice between 18–19 mo of age were divided into 6 groups to study effects of ISDN (0, 3 and 6 weeks) with and without exercise for the first 3 weeks of the experiment. Groups had 4–8 mice. Results in quadriceps muscle showed that ISDN treatment combined with exercise increased muscle mass, fiber CSA, and the protein-expression ratio of NOS-I/β-dystroglycan. ISDN for 6 wks also produced the greatest increase in SC activation. These findings show that combining NO treatment and exercise has the potential to combat age-related muscle atrophy. Supported by the Canadian Space Agency: Life Sciences