Stem cell secretome-treatment improves whole-body metabolism, reduces adiposity and promotes skeletal muscle function in aged mice
Aging coincides with the progressive loss of muscle mass and strength, increased adiposity, and diminished physical function. Accordingly, interventions aimed at improving muscle, metabolic, and/or physical health are of interest to mitigate the adverse effects of aging. In this study, we tested a stem-cell secretome product which contains a host of growth, cytoskeletal remodeling, and immunomodulatory factors. We examined the effects of 4 weeks of bi-weekly unilateral intramuscular secretome injections (quadriceps) in ambulatory aged male C57Bl/6 mice (22-23 months) compared to saline injected aged-matched controls. After 4 weeks of treatment, secretome delivery substantially increased whole body lean mass and decreased fat mass corresponding to higher fiber cross sectional area and smaller adipocyte size, respectively. Secretome-treated mice also displayed improved whole-body grip strength and rotarod performance and had higher energy expenditure and physical activity levels compared to control mice. Furthermore, secretome-treated mice had greater skeletal muscle Pax7+ cell abundance, capillary density, and collagen turnover. Finally, the secretome product reduced lipid content and lipid droplet size in adipocytes in vitro. These data suggest intramuscular treatment secretome improves whole-body metabolism, physical function, and remodels skeletal muscle and adipose tissue in aged mice. Overall design: Comparative gene expression of RNA-seq data following an acute injection of saline (control) and stem cell secretome product into the quadriceps of old (26-28 months) mice, n=10 per group.