Blunted hypertrophic response in old mouse muscle is associated with a lower satellite cell density and is not alleviated by resveratrol.

Background: Sarcopenia contributes to the decreased quality of life in the older person. While resistance exercise is an effective measure to increase muscle mass and strength, the hypertrophic response may be blunted in old age.

Objectives: To determine 1) whether hypertrophy in the m. plantaris of old mice was blunted compared to adult and 2) whether this was related to a reduced satellite cell (SC) density and 3) how resveratrol affects hypertrophy in old mice.

Methods: In adult (7.5 months, n=11), old (23.5 months, n=10) and old-resveratrol-treated (n=10) male C57BL/6J mice, hypertrophy of the left m. plantaris was induced by denervation of its synergists. The contralateral leg served as control.

Results: After six weeks, overload-induced myofiber hypertrophy and IIB-IIA shift in myofiber type composition were less pronounced in old than adult mice (P=0.03), irrespective of resveratrol treatment. Muscles from old mice had a lower SC density than adult muscles (P=0.002). Overload-induced SC proliferation (P<0.05) resulted in an increased SC density in old, but not adult muscles (P=0.02), while a decrease occurred after resveratrol supplementation (P=0.044). Id2 and myogenin protein expression levels were higher in old than adult muscles (P<0.05). Caspase-3 was expressed more in hypertrophied than control muscles and was reduced with resveratrol (P<0.05).

Conclusion: The blunted hypertrophic response in old mice was associated with a lower SC density, but there was no evidence for a lower capacity for proliferation. Resveratrol did not rescue the hypertrophic response and even reduced, rather than increased, the number of SCs in hypertrophied muscles.