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

Significance statement

Resveratrol is often promoted to reverse the age-related loss of muscle mass and function, and to enhance the gains in muscle mass and function induced by resistance training. We observed that resveratrol supplementation in mice did not have any effect on muscle function and did not alleviate the attenuated hypertrophic response in old mice. This suggests that resveratrol is not the miracle drug that restores muscle function or plasticity in old age.

Blunted hypertrophic response in old mouse muscle not alleviated by resveratrol-global medical discovery

Journal Reference

Ballak SB1, Jaspers RT2, Deldicque L3, Chalil S4, Peters EL2, de Haan A1, Degens H5. Exp Gerontol. 2015 Feb;62:23-31.

Show Affiliations

1School of Healthcare Science, Manchester Metropolitan University, Manchester, United Kingdom; Laboratory for Myology, MOVE Research Institute Amsterdam, Faculty of Human Movement Sciences, VU University Amsterdam, Amsterdam, The Netherlands.

2Laboratory for Myology, MOVE Research Institute Amsterdam, Faculty of Human Movement Sciences, VU University Amsterdam, Amsterdam, The Netherlands.

3Exercise Physiology Research Group, Department of Kinesiology, FaBeR, KU Leuven, Leuven, Belgium.

4Laboratory for Myology, MOVE Research Institute Amsterdam, Faculty of Human Movement Sciences, VU University Amsterdam, Amsterdam, The Netherlands; Exercise Physiology Research Group, Department of Kinesiology, FaBeR, KU Leuven, Leuven, Belgium.and

5School of Healthcare Science, Manchester Metropolitan University, Manchester, United Kingdom. Electronic address: [email protected]

Abstract

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.

Copyright © 2015 Elsevier Inc. All rights reserved.

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