Apoptosis in muscle atrophy: Relevance to sarcopenia

https://doi.org/10.1016/j.exger.2005.04.003Get rights and content

Abstract

The loss of muscle mass with aging, or sarcopenia, is an important contributor to the functional decline and loss of independence observed with aging. Little is known about the role of apoptosis in sarcopenia. Studies in adult animals have shown that apoptosis is involved in the loss of muscle nuclei during acute disuse atrophy, and caspase-3 dependent pathways play an important role in this process. Elevated apoptosis has also been observed in muscles of aged animals, but this does not depend upon caspase-3 pathways to the same extent as disuse atrophy. Moreover, disuse atrophy induced in aged animals is associated with a higher amount of apoptosis than in young and intracellular mechanisms are different from those in young, depending more on caspase-independent pathways. The functional relevance of the increase in apoptosis with respect to the loss of muscle fibers and muscle cross-sectional area with aging remains to be determined and interventions to decrease apoptosis in muscle need to be evaluated.

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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