IGF-I restores satellite cell proliferative potential in immobilized old skeletal muscle

One of the key factors responsible for the age-associated reduction in musc le mass may be that satellite cell proliferation potential (number of doubl ings contained within each cell) could become rate limiting to old muscle r egrowth. No studies have tested whether repeated cycles of atrophy-regrowth in aged animals deplete the remaining capacity of satellite cells to repli cate or what measures can be taken to prevent this from happening. We hypot hesized that there would be a pronounced loss of satellite cell proliferati ve potential in gastrocnemius muscles of aged rats (25- to 30-mo-old FBN ra ts) subjected to three cycles of atrophy by hindlimb immobilization (plaste r casts) with intervening recovery periods. Our results indicated that ther e was a significant loss in gastrocnemius muscle mass and in the proliferat ive potential of the resident satellite cells after just one bout of immobi lization. Neither the muscle mass nor the satellite cell proliferation pote ntial recovered from their atrophied values after either the first 3-wk or later 9-wk recovery period. Remarkably, application of insulin-like growth factor I onto the atrophied gastrocnemius muscle for an additional 2 wk aft er this 9-wk recovery period rescued similar to 46% of the lost muscle mass and dramatically increased proliferation potential of the satellite cells from this muscle.