Rejuvenation of Aged Muscle Stem Cells Through Exercise

Overview

The proposed study will establish a newly-identified signaling pathway regulating both autophagy and apoptosis in human satellite cells. These findings will allow for novel pharmacological targets in satellite cells to return regenerative capacity to elderly individuals. Up to 80 adults, 21 years of age and greater, will undergo a consent visit followed by three blood draws and muscle biopsy visits- baseline (pre), after the first exercise bout (post-acute), and after the 12 week training program (post-chronic). Blood will be obtained and tested for inflammatory (IL-6/TNF/IL-1) and endocrine markers (Testosterone/Estrogen/Thyroid hormone). As part of the intervention, participants will undergo moderate intensity treadmill exercise three times per week for 10-12 weeks or serve as sedentary controls. Muscle stem cell function will be compared across age groups at each time point using a One Way ANOVA or t test for specific comparisons. An alternative analysis will be a longitudinal design following muscle stem cell function from each individual before and after exercise training. This analysis will be performed with repeated measure ANOVAs. Data will be analyzed using GraphPad Prism 6 statistical software. Significance will be accepted as p\<.05. Thigh Muscle biopsies may result in momentary pain and discomfort, burning or bleeding, numbness, and rarely fainting or infection. The incision site may leave a scar and muscle soreness may be present up to ten days after the biopsy. While the local numbing medicine xylocaine is almost entirely free from allergic properties (such as causing hives), an allergic reaction is possible, and the participant will not be given xylocaine if they have a history of such a reaction. The xylocaine will be given by a small injection into the skin at the site of the muscle biopsy. Risks associated with a standard blood draw include momentary discomfort and/or bruising. In addition, there is a minimal risk of infection, excess bleeding, clotting, and fainting. An exercise program may result in muscle, bone and/or joint soreness, discomfort and/or injury. All collected data will be stored in a locked file to be accessed only by Dr. White and his study staff. Study records that identify subjects will be kept confidential as required by law.