Effects of (-)-epicatechin on molecular modulators of skeletal muscle growth and differentiation

Abstract

Sarcopenia is a notable and debilitating age-associated condition. Flavonoids are known for their healthy effects and limited toxicity. The flavanol (-)-epicatechin (Epi) enhances exercise capacity in mice, and Epi-rich cocoa improves skeletal muscle structure in heart failure patients. (-)-Epicatechin may thus hold promise as treatment for sarcopenia. We examined changes in protein levels of molecular modulators of growth and differentiation in young vs. old, human and mouse skeletal muscle. We report the effects of Epi in mice and the results of an initial proof-of-concept trial in humans, where muscle strength and levels of modulators of muscle growth were measured. In mice, myostatin and senescence-associated β-galactosidase levels increase with aging, while those of follistatin and Myf5 decrease. (-)-Epicatechin decreases myostatin and β-galactosidase and increases levels of markers of muscle growth. In humans, myostatin and β-galactosidase increase with aging while follistatin, MyoD and myogenin decrease. Treatment for 7 days with (-)-epicatechin increases hand grip strength and the ratio of plasma follistatin/myostatin. In conclusion, aging has deleterious effects on modulators of muscle growth/differentiation, and the consumption of modest amounts of the flavanol (-)-epicatechin can partially reverse these changes. This flavanol warrants its comprehensive evaluation for the treatment of sarcopenia.

Keywords: Epicatechin; Flavonoids; Sarcopenia.

© 2014.

Figures

Figure 1

Differences observed in SkM growth/differentiation and SA-β-Gal protein levels in young and old control or (−)-epicatechin treated mice. Panel A shows Western blot images observed in myostatin, follistatin, MEF2A, Myf5, MyoD, myogenin. Panel B plots the mean ± SEM densitometric units of the protein of interest normalized over GAPDH values. Panel C denotes differences observed in senescence associated-β-Gal protein levels. (n=5/group).

Figure 2

Differences observed in markers of muscle growth, in older vs. young human subjects, and effects of 1 week (−)-epicatechin treatment on strength and SkM growth markers in middle age subjects. Panel A shows Western blot images for myostatin, follistatin, MEF2A, Myf5, MyoD, myogenin protein levels in human quadriceps from young vs. old subjects. Panel B plots the mean ± SEM densitometric units of the protein of interest normalized over GAPDH values. Panel C denotes differences observed in senescence associated-β-Gal protein levels. (n=5/group).