Abstract

Sarcopenia is an age-related loss of muscle mass and strength. The aged can increase various measures of muscle size and strength in response to resistance exercise (RE), but this may not normalize specific tension. In rats, aging reduces the hypertrophy response and impairs regeneration. In this study, we measured cellular and molecular markers, indicative of muscle hypertrophy, that also respond to acute increases in loading. Comparing 6- and 30-mo-old rats, the aims were to 1) determine whether these markers are altered with age and 2) identify age-sensitive responses to acute RE. The muscles of old rats exhibited sarcopenia involving a deficit in contractile proteins and decreased force generation. The RNA-to-protein ratio was higher in the old muscles, suggesting a decrease in translational efficiency. There was evidence of reduced signaling via components downstream from the insulin/insulin-like growth factor (IGF)-I receptors in old muscles. The mRNA levels of myostatin and suppressor of cytokine signaling 2, negative regulators of muscle mass, were lower in old muscles but did not decrease following RE. RE induced increases in the mRNAs for IGF-I, mechano-growth factor, cyclin D1, and suppressor of cytokine signaling 3 were similar in old and young muscles. RE induced phosphorylation of the IGF-I receptor, and Akt increased in young but not old muscles, whereas that of S6K1 was similar for both. The results of this study indicate that a number of components of intracellular signaling pathways are sensitive to age. As a result, key anticatabolic responses appear to be refractory to the stimuli provided by RE.

Highlights

  • Compared with the Sol, vastus intermedius, and PLN muscles, the relative mass of the medial gastrocnemius (MG) muscle exhibited the greatest degree of sarcopenia, being 46% smaller in the old vs. young rats (Table 1)

  • In addition to the overall decreased muscle size seen with aging, the MG muscles of the old rats exhibited an exaggerated loss of contractile proteins (Table 2)

  • The disproportionate loss of contractile proteins appeared to manifest, at least partially, as a loss of myosin heavy chain (MHC) protein (Table 2). These findings are in general agreement with the results from a number of human studies that have found a dramatic decrease in mixed muscle- and MHC-protein synthesis with age [63, 93]

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Summary

Introduction

AGE-RELATED DECREASES IN MUSCLE STRENGTH result in decrements in performance that negatively impact health and the quality of life in aged humans The results of cross-sectional studies suggest that sarcopenia is a major determinant of aging-associated decrements in strength Postmortem studies of whole muscle cross sections (vastus lateralis) have found that sarcopenia results from both a loss of myofibers and a decrease in type II fiber size [49]. As in studies of aged humans, many animal studies have reported that, in commonly studied antigravity muscles [vastus lateralis, gastrocnemius, plantaris (PLN), soleus (Sol)] of Fisher 344/Brown Norway F1 cross (F/BN) rats, sarcopenia is most pronounced in fast muscles [14, 25, 56]. Mercier et al [58] found that Sol muscles of older rats experienced the same degree of atrophy as that of younger animals in response to denervation

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