Review ArticleModulation of age-induced apoptotic signaling and cellular remodeling by exercise and calorie restriction in skeletal muscle
Section snippets
Pathophysiology and clinical significance of apoptosis and apoptotic signaling in aging skeletal muscle
An age-related loss of muscle mass and function occurs in skeletal muscle of a variety of species; this process is referred to as sarcopenia of aging and is reflected by a 25–35% decrease in the cross-sectional area of several limb muscles due to atrophy and loss of muscle fiber [1]. This large decline has significant public health ramifications, because it has been reported that impaired muscle strength is highly predictive of falls, disability, and all-cause mortality in advanced age [2], [3]
Modulation of apoptotic signaling by treadmill exercise
Apoptosis or programmed cell death is highly conserved across species, tightly regulated, and executed via activation of specific signaling pathways. One key characteristic of apoptosis is that it results in the death of a single cell without inducing inflammation and therefore potential disruption in surrounding tissues [25], [31]. However, it should be noted that in multinucleated skeletal muscle, proapoptotic signaling may result in other fates in addition to cell death. Indeed, apoptotic
Modulation of apoptotic signaling in skeletal muscle by calorie restriction
The precise mechanisms by which calorie restriction (CR; 30–40%) delays the aging process still remain to be fully elucidated. However, CR is intricately involved in regulating cellular and systemic redox status and in modulating the expression of genes related to macromolecule and organelle turnover, energy metabolism, and cell death and survival [19], [57], [58]. For example, CR attenuates induction of inflammatory genes [59] which may be associated with both inner- and extracellular
Combining lifelong voluntary exercise and mild calorie restriction: pragmatic rodent model for human prevention of sarcopenia?
There is growing interest in using lifelong exercise approaches as a model to reduce the risk for sarcopenia and age-associated chronic diseases (i.e., heart disease, hypertension, type II diabetes), for which a sedentary lifestyle represents a significant risk factor [74]. Traditionally, resistive exercise is thought to be the most efficient approach to promoting muscle hypertrophy and to prevent atrophy in young and middle-age subjects [75]. However, some evidence in the gerontology
Conclusions
Age-related skeletal muscle loss is associated with multiple adverse outcomes, including increased incidence of disability and overall mortality. Sarcopenia is a highly prevalent condition among older adults and is responsible for a considerable health care expenditure. Yet, little is known about the mechanisms involved in skeletal muscle loss with age and potential treatments for sarcopenia.
Accumulating evidence suggests that acceleration of skeletal muscle apoptosis due to chronic
Acknowledgments
This research was supported by grants to C.L. from the National Institute on Aging (R01-AG17994 and AG21042) and to J.L. (American Heart Association–Texas Affiliate No. GIA 0555064Y and NIH R03; 1R03AR054084-01) and to A.Y.S. (American Heart Association Fellowship 0615256B). The research of Drs. Marzetti and Manini is supported by the Claude D. Pepper Older Americans Independence Center (1 P30 AG028740-01).
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These authors contributed equally to this work.