Sarcopenia is an age-associated decline of skeletal muscle mass and function and is known to lead to frailty, cachexia, osteoporosis, metabolic syndromes, and death. Notwithstanding the increasing incidence of sarcopenia, the molecular and cellular mechanisms driving age-related sarcopenia are not completely understood. This article reviews current definitions of sarcopenia, its potential mechanisms, and effects of exercise on sarcopenia. The pathogenesis of age-related sarcopenia is multifactorial and includes myostatin, inflammatory cytokines, and mitochondria-derived problems. Especially, age-induced mitochondrial dysfunction triggers the production of reactive oxygen species (ROS) by mitochondria, impedes mitochondrial dynamics, interrupts mitophagy, and leads to mitochondria-mediated apoptosis. Aerobic exercise provides at least a partial solution to sarcopenia as it ameliorates mitochondria-derived problems, and resistance exercise strengthens muscle mass and function. Furthermore, combinations of these exercise types provide the benefits of both. Collectively, this review summarizes potential mechanisms of age-related sarcopenia and emphasizes the use of exercise as a therapeutic strategy, suggesting that combined exercise provides the most beneficial means of combating age-related sarcopenia.

Seo DY, et al. Korean J Physiol Pharmacol. 2018 May;22(3):235-248. https://doi.org/10.4196/kjpp.2018.22.3.235

Sarcopenia has been defined as a progressive decline of skeletal muscle mass, strength, and functions in elderly people. It is accompanied by physical frailty, functional disability, falls, hospitalization, and mortality, and is becoming a major geriatric disorder owing to the increasing life expectancy and growing older population worldwide. Experimental models are critical to understand the pathophysiology of sarcopenia and develop therapeutic strategies. Although its etiologies remain to be further elucidated, several mechanisms of sarcopenia have been identified, including cellular senescence, proteostasis imbalance, oxidative stress, and “inflammaging.” In this article, we address three main aspects. First, we describe the fundamental aging mechanisms. Next, we discuss both in vitro and in vivo experimental models based on molecular mechanisms that have the potential to elucidate the biochemical processes integral to sarcopenia. The use of appropriate models to reflect sarcopenia and/or its underlying pathways will enable researchers to understand sarcopenia and develop novel therapeutic strategies for sarcopenia. Lastly, we discuss the possible molecular targets and the current status of drug candidates for sarcopenia treatment. In conclusion, the development of experimental models for sarcopenia is essential to discover molecular targets that are valuable as biochemical biomarkers and/or therapeutic targets for sarcopenia.

The aging process in skeletal muscle is characterized by a loss of myocytes and reduction in cross-sectional area of the remaining myocytes, particularly in Type II (fast-twitch) muscle fibers. In multinucleated skeletal muscle, apoptosis may contribute to both fiber atrophy and loss of muscle fibers. Recent evidence suggests that the mitochondrial Bcl-2 family pathway may be a target of aging. Here the authors demonstrated that aging increased DNA fragmentation, cleaved caspase-3, and pro-apoptotic Bax in rat skeletal muscle. Twelve weeks of treadmill exercise training increased anti-apoptotic Bcl-2, while markedly reducing DNA fragmentation, and cleaved caspase-3, Bax, and Bax/Bcl-2 ratio in the white gastrocnemius and soleus muscles of old rats. Upstream anti-apoptotic NF-κB activity decreased in aging skeletal muscle, and increased with exercise training. Regulation of NF-κB activity with aging and exercise was not related to changes in NF-κB subunit protein levels. Instead, changes in post-translational activation of NF-κB occurred as a function of altered phosphorylation of IκB. These results indicate that treadmill exercise training attenuates fiber atrophy and pro-apoptotic signaling in aging skeletal muscle.