Blunted angiogenesis and hypertrophy are associated with increased fatigue resistance and unchanged aerobic capacity in old overloaded mouse muscle.

Sam B Ballak,Hans Degens,Arnold De Haan,Richard T Jaspers,Tinelies Busé-Pot,Moi H Yap,Peter J Harding,Louise Deldicque

doi:10.1007/s11357-016-9894-1

Abstract

We hypothesize that the attenuated hypertrophic response in old mouse muscle is (1) partly due to a reduced capillarization and angiogenesis, which is (2) accompanied by a reduced oxidative capacity and fatigue resistance in old control and overloaded muscles, that (3) can be rescued by the antioxidant resveratrol. To investigate this, the hypertrophic response, capillarization, oxidative capacity, and fatigue resistance of m. plantaris were compared in 9- and 25-month-old non-treated and 25-month-old resveratrol-treated mice. Overload increased the local capillary-to-fiber ratio less in old (15 %) than in adult (59 %) muscle (P < 0.05). Although muscles of old mice had a higher succinate dehydrogenase (SDH) activity (P < 0.05) and a slower fiber type profile (P < 0.05), the isometric fatigue resistance was similar in 9- and 25-month-old mice. In both age groups, the fatigue resistance was increased to the same extent after overload (P < 0.01), without a significant change in SDH activity, but an increased capillary density (P < 0.05). Attenuated angiogenesis during overload may contribute to the attenuated hypertrophic response in old age. Neither was rescued by resveratrol supplementation. Changes in fatigue resistance with overload and aging were dissociated from changes in SDH activity, but paralleled those in capillarization. This suggests that capillarization plays a more important role in fatigue resistance than oxidative capacity.

Highlights

Aging is accompanied by a progressive decline in muscle mass and power (Roseberg 1989)
Muscle fatigue resistance during intermittent isometric contractions is related to the oxidative capacity of single muscle fibers and motor units (Degens and Veerkamp 1994), and as aerobic metabolism requires an adequate supply of oxygen via the capillaries, it is not surprising that fatigue resistance is positively related to muscle capillarization (Hudlicka et al 1977)
The age-related rate of decline in VO2max accelerates with increasing age (Fleg et al 2005) and while superfluous capillarization may be a late hallmark of skeletal muscle aging, it is not known whether (1) this is the case during early stages of sarcopenia, nor (2) how early age-related changes in aerobic capacity and capillarization affect muscle fatigue resistance

Summary

Introduction

Aging is accompanied by a progressive decline in muscle mass (sarcopenia) and power (Roseberg 1989). Together, these changes will limit the ability to perform daily life. Aerobic power of skeletal muscle is reduced, even when convective oxygen delivery was matched in young and old muscles (Hepple et al 2003) Such a situation can occur due to a lower oxidative enzyme activity and/or a diminished muscle capillarization, which both have been observed in aged humans (Coggan et al 1992; Degens 1998; Hepple et al 1997; Konopka et al 2014) and rats (Degens et al 1993b; Skorjanc et al 2001). The age-related rate of decline in VO2max accelerates with increasing age (Fleg et al 2005) and while superfluous capillarization may be a late hallmark of skeletal muscle aging, it is not known whether (1) this is the case during early stages of sarcopenia, nor (2) how early age-related changes in aerobic capacity and capillarization affect muscle fatigue resistance

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