Abstract

Older men (n = 12) and women (n = 18) 65–80 years of age completed 12 weeks of exercise and took either a placebo or resveratrol (RSV) (500 mg/d) to test the hypothesis that RSV treatment combined with exercise would increase mitochondrial density, muscle fatigue resistance, and cardiovascular function more than exercise alone. Contrary to our hypothesis, aerobic and resistance exercise coupled with RSV treatment did not reduce cardiovascular risk further than exercise alone. However, exercise added to RSV treatment improved the indices of mitochondrial density, and muscle fatigue resistance more than placebo and exercise treatments. In addition, subjects that were treated with RSV had an increase in knee extensor muscle peak torque (8%), average peak torque (14%), and power (14%) after training, whereas exercise did not increase these parameters in the placebo-treated older subjects. Furthermore, exercise combined with RSV significantly improved mean fiber area and total myonuclei by 45.3% and 20%, respectively, in muscle fibers from the vastus lateralis of older subjects. Together, these data indicate a novel anabolic role of RSV in exercise-induced adaptations of older persons and this suggests that RSV combined with exercise might provide a better approach for reversing sarcopenia than exercise alone.

Keywords: Mitochondria, Sarcopenia, Fiber type, Exercise, Muscle, Strength, Fatigue

Sarcopenia is predictive of falls and is associated with periods of hospital-associated immobilization (1). This is noteworthy, as aging muscles display an impaired or failed recovery following immobilization-induced muscle atrophy (2,3). Several potential countermeasures to unloading-induced atrophy have been tested, but most have only been partially successful. For example, taurine was shown to prevent the slow to fast myosin shift with unloading (4), but it did not prevent the loss of muscle mass. Insulin growth factor-I overexpression during hindlimb unloading in rodents induced some potential molecular signaling improvements, especially the atrogen Muscle RING-finger protein-1 (MuRF1), but there was no overall change in muscle protein loss or fiber type transition with this treatment (5). In addition, β-hydroxy-β-methylbutyrate, a leucine metabolite, provided modest protection against skeletal loss of muscle mass during disuse in sarcopenic rats (6). We have found that green tea extract increased satellite cell proliferation and differentiation in rat plantaris and soleus muscles during recovery from hindlimb suspension as compared to vehicle-treated muscles and decreased oxidative stress and the abundance of the Bcl-2–associated X protein (Bax), a proapoptotic protein, yet this did not further improve muscle recovery in [Public domain], via Wikimedia Commonsreloaded muscles over placebo (PL) treatments (7).

In vitro studies have shown that resveratrol (3,5,4′-trihydroxystilbene; RSV) increases protein synthesis (8), inhibits protein degradation, and attenuates atrophy of skeletal muscle fibers (9–12). A high dose of RSV in vivo (400 mg/kg/d) was reported to attenuate muscle fiber atrophy following hindlimb suspension (13) in rodents. We have found that a low dose (12.5 mg/kg/d) of RSV (14) had a trend (p = .06) to blunt the loss of muscle mass during hindlimb suspension in old rats but it did not improve recovery or increase the number of satellite cells or muscle mass after

disuse in old animals (15). Nevertheless, other data failed to identify RSV-mediated improvements in metabolic function in rodents (16). Furthermore, while exercise adaptations in the elderly are typically attenuated as compared to responses in young adults (17), it is not known if RSV coupled to exercise provides a stronger stimulus for reducing or reversing sarcopenia in humans (18) than exercise alone.

Thus, the purpose of this study was to determine if 12 weeks of exercise would improve muscle fatigue resistance more than exercise alone in older men and women. We tested the hypothesis that RSV treatment would increase mitochondrial density, which would decrease muscle fatigue resistance, and improve indices for cardiovascular risk as compared to exercise alone in older men and women.

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