Skeletal muscle gene expression profiles in 20–29 year old and 65–71 year old women
Introduction
Sarcopenia, the decline in muscle mass and function associated with aging, limits independence, reduces the quality of life, and increases the probability of falling. Because women have less muscle mass and strength than men, this problem is especially significant in older women. A gradual loss of motor neurons is thought to be an important determinant of muscle fiber loss in old age, even though sprouting of motor nerve axons can re-innervate and rescue many of the denervated fibers (Lexell, 1997, Luff, 1998). Age-related changes in hormone and cytokine levels probably have some role in sarcopenia (Lamberts et al., 1997, Roubenoff, 2003). Oxidative damage to proteins and DNA also might be responsible for cell loss or dysfunction (Mecocci et al., 1999). A reduction in physical activity with aging may contribute to muscle fiber atrophy and altered metabolic activity of muscle in some persons, although muscle mass and function decline with aging even in the most active individuals (references cited in Welle, 2002).
The ultimate effects of denervation, reactive oxygen species, hormonal changes, and behavioral changes on muscle mass and function depend to a large extent on the expression of genes required for tissue homeostasis or adaptation to patterns of contractile activity. Gene expression profiling technology permits the parallel assessment of expression levels of thousands of genes, and may lead to a better understanding of the molecular basis of sarcopenia and other age-related problems. Most previous studies of the effect of aging on muscle gene expression profiles did not include women (Jozsi et al., 2000, Welle et al., 2000, Welle et al., 2002b). Roth et al. (2002) included both men and women in their filter array study of aging in human skeletal muscle (∼1000 genes). However, because individual RNA samples were pooled, they could not determine the statistical significance of the apparent age-related differences in women. Because women and men differ in hormone levels and certain characteristics of muscle (Coggan et al., 1992, Frontera et al., 2000, Hunter and Enoka, 2001, Simoneau and Bouchard, 1989, Staron et al., 2000), it cannot be assumed that they have identical age-related changes in muscle. Thus, the present study was done to determine the effect of aging on muscle gene expression profiles in women.
Section snippets
Methods
The subjects were seven young (20–29 years old) and eight older (65–71 years old) women. All were healthy according to blood tests, history, and physical examination. Subjects signed a consent form after risks were explained. The project was approved by the University of Rochester Research Subjects Review Board.
The subjects were not engaged in any type of regular exercise program involving strenuous activity for more than 2 h per week, nor did they perform any high-resistance exercises
Results
As expected, older women who had less lean tissue mass, were weaker, and had a lower peak rate of oxygen consumption (Table 1). However, isometric knee extension strength per kg leg lean tissue mass was similar in younger and older women. There was no significant effect of age (P>0.20) on patterns of expression of the major adult MyHC isoforms, types 1, 2a, and 2x (data not shown).
The gene expression profiles of each individual have been deposited in the National Center for Biotechnology
Discussion
The gene expression profiles of older women suggest that their muscles detect an increased amount of DNA damage relative to young muscles. One of the most highly overexpressed genes (↑ 4-fold) is p21, a cyclin-dependent kinase inhbitor that is overexpressed in response to DNA damage (Hattinger et al., 2002, Kaufmann and Paules, 1996). An age-related increase in p21 expression also was observed in muscle of men (↑ 2.9-fold) (Welle et al., 2003) and monkeys (↑ 4.1-fold) (Kayo et al., 2001). In
Acknowledgements
We thank Don Henderson and Catherine Muzytchuk for technical assistance. SAM software, version 1.12, was provided by Stanford University. The project was supported by grants from the NationaI Institutes of Health, AG-17891, AG-18254, RR-00044, and AR/NS-48143.
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