Modulation of age-induced apoptotic signaling and cellular remodeling by exercise and calorie restriction in skeletal muscle

doi:10.1016/j.freeradbiomed.2007.05.028

Free Radical Biology and Medicine

Volume 44, Issue 2, 15 January 2008, Pages 160-168

https://doi.org/10.1016/j.freeradbiomed.2007.05.028 Get rights and content

Abstract

Aging is inevitably associated with a progressive loss of muscle mass and strength, a condition also known as sarcopenia of aging. Although the precise mechanisms underlying this syndrome have not been completely elucidated, recent studies point toward several key cellular mechanisms that could contribute to age-associated muscle loss. Among these, mitochondrial dysfunction and deregulation of apoptotic signaling have emerged as critical players in the onset and progression of sarcopenia. Interestingly, calorie restriction, a well-known antiaging intervention, and, more recently, exercise training have been shown to beneficially affect both mitochondrial function and apoptotic signaling in skeletal muscle from young and old animals. Preliminary observations also indicate that even a small (8%) reduction in food intake may still provide protective effects against sarcopenia and cellular remodeling in aging skeletal muscle, with the advantage of being more applicable to human subjects than the traditional 30–40% restriction regimen. The most recent evidence on the relevance of skeletal muscle apoptosis to sarcopenia, as well as its modulation by calorie restriction and exercise, is reviewed.

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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¹: These authors contributed equally to this work.

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Review ArticleModulation of age-induced apoptotic signaling and cellular remodeling by exercise and calorie restriction in skeletal muscle

Abstract

Section snippets

Pathophysiology and clinical significance of apoptosis and apoptotic signaling in aging skeletal muscle

Modulation of apoptotic signaling by treadmill exercise

Modulation of apoptotic signaling in skeletal muscle by calorie restriction

Combining lifelong voluntary exercise and mild calorie restriction: pragmatic rodent model for human prevention of sarcopenia?

Conclusions

Acknowledgments

J. Neurol. Sci.

Mech. Ageing Dev.

Mech. Ageing Dev.

Brain Res.

J. Neurol. Sci.

Free Radic. Biol. Med.

Biochim. Biophys. Acta

Mech. Ageing Dev.

Lancet

J. Am. Coll. Cardiol.

Exp. Gerontol.

Pharmacol. Ther.

FEBS Lett.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Nutr.

Free Radic. Biol. Med.

Mech. Ageing Dev.

Clin. Geriatr. Med.

Am. J. Clin. Nutr.

Human aging, muscle mass, and fiber type composition

J. Gerontol. A Biol. Sci. Med. Sci.

Midlife hand grip strength as a predictor of old age disability

JAMA

Skeletal muscle strength as a predictor of all-cause mortality in healthy men

J. Gerontol. A Biol. Sci. Med. Sci.

Disability in older adults: evidence regarding significance, etiology, and risk

J. Am. Geriatr. Soc.

Thigh composition in young and elderly men determined by computed tomography

Clin. Physiol.

The size and strength of the quadriceps muscles of old and young men

Clin. Physiol.

Early-onset calorie restriction conserves fiber number in aging rat skeletal muscle

FASEB J.

Growth hormone supplementation increases skeletal muscle mass of old male Fischer 344/Brown Norway rats

J. Gerontol. A Biol. Sci. Med. Sci.

Viral mediated expression of insulin-like growth factor I blocks the aging-related loss of skeletal muscle function

Proc. Natl. Acad. Sci. USA

What insights into age-related changes in skeletal muscle are provided by animal models?

J. Gerontol. A Biol. Sci. Med. Sci.

Mitochondrial DNA deletion mutations: a causal role in sarcopenia

Eur. J. Biochem.

Apoptosis in skeletal muscle with aging

Am. J. Physiol. Regul. Integr. Comp. Physiol.

Factors influencing the repair and adaptation of muscles in aged individuals: satellite cells and innervation

J. Gerontol. A Biol. Sci. Med. Sci.

Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging

Science

Mitochondrial DNA deletion mutations colocalize with segmental electron transport system abnormalities, muscle fiber atrophy, fiber splitting, and oxidative damage in sarcopenia

FASEB J.

Mitochondrial abnormalities are more frequent in muscles undergoing sarcopenia

J. Appl. Physiol.

A pattern of accumulation of a somatic deletion of mitochondrial DNA in aging human tissues

Proc. Natl. Acad. Sci. USA

Apoptosis and aging: role of the mitochondria

J. Gerontol. A Biol. Sci. Med. Sci.

Exercise training attenuates age-induced changes in apoptotic signaling in rat skeletal muscle

Antioxid. Redox Signaling

Review Article
Modulation of age-induced apoptotic signaling and cellular remodeling by exercise and calorie restriction in skeletal muscle