Attenuation of age-related sarcopenia by creatine supplementation has been equivocal. In this study, plantaris muscles of young (Y; 5m) and aging (A; 24m) Fisher 344 rats underwent four weeks of either control (C), creatine supplementation (Cr), surgical overload (O), or overload plus creatine (OCr). Creatine alone had no effect on muscle fiber cross-sectional area (CSA) or heat shock protein (HSP70) and increased myonuclear domain (MND) only in young rats. Overload increased CSA and HSP70 content in I and IIA fibers, regardless of age, and MND in IIA fibers of YO rats. CSA and MND increased in all fast fibers of YOCr, and CSA increased in I and IIA fibers of AOCr. OCR did not alter HSP70, regardless of age. MND did not change in aging rats, regardless of treatment. These data indicate creatine alone had no significant effect. Creatine with overload produced no additional hypertrophy relative to overload alone and attenuated overload-induced HSP70 expression. 1. Introduction Aging is associated with reductions in skeletal muscle mass and strength (sarcopenia), which may lead to impaired mobility in older individuals. Despite a litany of research on sarcopenia, the underlying mechanisms remain to be elucidated. Comprehensive reviews of the potential mechanisms behind sarcopenia are available (e.g., Ryall et al. 2008 [1]). In brief, declines in muscle-specific stem cells (satellite cells); increases in myostatin, a negative regulator of muscle growth; changes in circulating hormone levels; impairment of neuromuscular function; increased myonuclear apoptosis have all been proposed as mechanisms underlying sarcopenia. Creatine (C4H9N3O2) supplementation is a popular dietary supplement with recreational and professional athletes. It has been shown to increase exercise performance [2, 3] and strength [4]. Creatine is a naturally occurring molecule in skeletal muscle and can be synthesized or obtained in the diet. Creatine and phosphocreatine (PCr) are involved in coupling anaerobic metabolism with ATP demand [5]. Increased intramuscular levels of PCr may permit increased temporal buffering of ATP during high-intensity muscle contraction, and increased creatine levels may allow increased PCr resynthesis [6]. In so doing, creatine supplementation may indirectly increase muscle mass and strength by allowing training at higher workloads [7]. However, the mechanisms behind the enhancement of performance and increases in muscle strength by creatine supplementation have not been fully elucidated. The use of a dietary supplement, such as creatine, to counteract
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