Apoptosis in muscle atrophy: Relevance to sarcopenia
Section snippets
Skeletal muscle atrophy and sarcopenia
Skeletal muscle mass declines with advancing age, such that by 60–70 years of age, skeletal muscle mass in humans has decreased by 25–30%, resulting in a significant decrease of muscle strength. The functional impairment resulting from this age-associated loss of muscle mass, i.e. sarcopenia, has far reaching consequences for the elderly: their ability to successfully participate in physical activities and to perform tasks of daily living is impaired and muscle weakness has been found to be a
Apoptosis
Apoptosis, or programmed cell death, is an important process during development in multicellular organisms ensuring the elimination of superfluous tissues, such as webbing between digits, and is also critical for maintenance of tissue homeostasis in adults. The early stage of apoptosis involves death-inducing signals, such as reactive oxygen and nitrogen species, ligands for the death receptors, among which tumor necrosis factor (TNF)-α, imbalances in calcium regulation, and alterations in the
Apoptotic pathways involved in adult muscle atrophy
Some of the above-mentioned pathways have been investigated in skeletal muscles from adult animals during atrophy. Caspase-3 activity or activated caspase-3 protein abundance was increased in correlation with apoptosis in models of muscle atrophy, such as after burns, in chronic heart failure and with hind limb suspension (Dalla Libera et al., 1999, Leeuwenburgh et al., 2005, Yasuhara et al., 2000) and caspase-3 was also involved in the induction of apoptosis in myotubes in vitro (McArdle et
Sarcopenia and apoptosis
With respect to aging, the question arises whether apoptosis plays a role in sarcopenia. As mentioned previously, the decline in muscle mass and function during aging results from the loss of muscle fibers as well as a loss of cross-sectional area (atrophy) of remaining fibers, unlike acute muscle atrophy which is mainly due to a decrease in muscle fiber area. It has been suggested that oxidative stress and consequently mitochondrial DNA (mtDNA) mutations play a causal role in the loss of
Disuse atrophy in aged skeletal muscle and the role of apoptosis
As discussed above, apoptosis is associated with acute muscle atrophy in adult animals, where it is responsible for the removal of nuclei to maintain a relatively constant myonuclear domain, and apoptosis is also correlated with age-related atrophy. The question arises whether the process of apoptosis and nuclear loss is similar in old and young animals during acute muscle atrophy. The extent of nuclear loss during atrophy is important since recovery of muscle mass is not complete if nuclear
Summary and directions for future research
The role of apoptosis in age-related and disuse-related muscle loss is starting to be explored, but is still uncertain. Apoptosis is very likely involved in the loss of muscle nuclei with disuse, but whether it is also responsible for the loss of actual muscle fibers with aging (sarcopenia) needs to be further investigated. Furthermore, it seems that pathways employed by muscles undergoing disuse atrophy are different between old and young animals, but the functional significance of this
Acknowledgements
The author would like to acknowledge the following research grants for funding: NIH/NIAMS AR47577 and NIH/NIA AG20407.
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2021, Experimental GerontologyCitation Excerpt :In male Wistar rats, hindlimb muscle mass also progressively declined with age, reaching approximately 50% atrophy by 24 months of age compared with controls at 8 months of age (Pannérec et al., 2016). While many mechanisms, such as mitochondrial dysfunction (Marzetti et al., 2013), increased apoptosis (Dupont-Versteegden, 2005), suppression of satellite cell function (Fukada, 2018), increased reactive oxygen species (Gomes et al., 2017), and abnormal regulation of autophagy (Jiao and Demontis, 2017), have been reported, the onset mechanism of sarcopenia has not been identified in detail yet (Wagatsuma and Sakuma, 2012; McCormick and Vasilaki, 2018). Skeletal muscle mainly comprises multinucleated muscle fibers.