Elsevier

Ageing Research Reviews

Volume 24, Part B, November 2015, Pages 166-177
Ageing Research Reviews

Review
17β-Estradiol and testosterone in sarcopenia: Role of satellite cells

https://doi.org/10.1016/j.arr.2015.07.011Get rights and content

Highlights

  • 17β-Estradiol and testosterone regulate satellite cells physiology.

  • Role of satellite cells in sarcopenia.

  • 17β-Estradiol and testosterone modulate apoptosis in satellite cells.

Abstract

The loss of muscle mass and strength with aging, referred to as sarcopenia, is a prevalent condition among the elderly. Although the molecular mechanisms underlying sarcopenia are unclear, evidence suggests that an age-related acceleration of myocyte loss via apoptosis might be responsible for muscle perfomance decline. Interestingly, sarcopenia has been associated to a deficit of sex hormones which decrease upon aging. The skeletal muscle ability to repair and regenerate itself would not be possible without satellite cells, a subpopulation of cells that remain quiescent throughout life. They are activated in response to stress, enabling them to guide skeletal muscle regeneration. Thus, these cells could be a key factor to overcome sarcopenia. Of importance, satellite cells are 17β-estradiol (E2) and testosterone (T) targets. In this review, we summarize potential mechanisms through which these hormones regulate satellite cells activation during skeletal muscle regeneration in the elderly. The advance in its understanding will help to the development of potential therapeutic agents to alleviate and treat sarcopenia and other related myophaties.

Introduction

Aging is an inevitable biological process characterized by the progressive deterioration of numerous tissues and their physiological functions (Young, 1997). Specifically, with regards to skeletal muscle, senescence implies a progressive loss of its performance (Evans, 1995) affecting the daily movements and independence in the elderly (Rantanen et al., 2002, Sinha-Hikim et al., 2003). One of the most striking effects of aging on muscle is the gradual loss of skeletal muscle mass and its associated loss of strength, also referred to as sarcopenia (Cruz-Jentoft et al., 2010). It is really a prime component of frailty syndrome, affecting radically the functional capacity, mobility and general health in adult people resulting in a poor quality of life and increased mortality (Fielding et al., 2011, Marzetti and Leeuwenburgh, 2006). Although there are several diagnostic criteria for sarcopenia, the general consensus indicates the evaluation of the presence of low muscle mass along with low muscle function (Cruz-Jentoft et al., 2010, Fielding et al., 2011, Morley et al., 2011, Muscaritoli et al., 2010).

Similar to other age-related conditions, sarcopenia is characterized by a multifactorial etiology, in which neuronal (Vandervoort, 2002) and hormonal (Szulc et al., 2004) alterations, high levels of catabolic cytokines (Visser et al., 2002), nutritional disorders (Dreyer and Volpi, 2005) and decreased physical activity (Szulc et al., 2004) are the key causal factors responsible of this pathology. However, the specific contribution of each of these factors and the molecular mechanisms triggered by those conditions that ultimately lead to fiber loss, are still largely unknown.

In humans, skeletal muscle is one of the most abundant tissues in the body. It is composed of bundles of fibers (muscle cells) named as fascicles. The cell membrane surrounding the muscle fiber is the sarcolemma, and under this membrane lies the sarcoplasm, containing proteins, organelles, and myofibrils: the actin and myosin filaments. The arrangement of actin (the thin filaments) and myosin (the thick filaments) gives skeletal muscle its striated appearance (review in Scott et al., 2001). In addition, skeletal muscle is an extremely heterogeneous tissue, composed of a large variety of fiber types (McComas, 1996, Pette and Staron, 1997) that are classified based on histochemical, biochemical, morphological and physiological characteristics. However, classifications of muscle fibers by different techniques do not always agree (Staron, 1997). The composition of myosin heavy chain isoforms in the fiber is the determinant of muscle fiber type. Type I fibers have a predominance of myosin heavy chain 1 (MHC1). They are slow-twitch fatigue resistant fibers with greater oxidative capacity, higher mitochondrial content, and a greater capillary density. While type IIA fibers have a predominance of myosin heavy chain 2a (MHC2a), in type IIB fibers prevail myosin heavy chain 2x (MHC2x). The type II fibers are fast-twitch fibers with a high glycolytic capacity. The type IIA ones have intermediate oxidative and glycolytic capacity and are more fatigue resistant, whereas type IIB and IIC are more glycolytic. The differences in the mitochondrial content between fiber types could be responsible of the degree of susceptibility to aged deterioration of each skeletal muscle fiber type.

Skeletal muscle cross-sectional area decreases with normal aging, and its fiber distribution shifts to a slower profile. Endurance decrease can be due to a reduced number of mitochondria and a subsequent reduction in mitochondrial enzymes (Essen-Gustavsson and Borges, 1986). In agreement, Lexell et al. (1988) clearly showed that both, types I and II muscle fibers, are lost with aging. Nevertheless, others indicate that the impact of age on muscle is fiber type specific (Grimby, 1995, Hortobagyi et al., 1995, Klitgaard et al., 1990, Mc Kiernan et al., 2012, Singh et al., 1999). Accordingly, it has been shown an increased proportion of type I muscle fibers at advanced age, implying the predominant loss of type II fibers (Dreyer et al., 2006, Larsson et al., 1978). However, the most reliable findings are the decline in the total number of muscle fibers and the specific atrophy of the type II fibers, both contributing to sarcopenia (Grimby, 1995, Lexell et al., 1988, Nilwik et al., 2013). Furthermore, fiber type grouping (Lexell et al., 1988) and decreased capillarization have been observed in aged muscle tissue (Frontera et al., 2000). The knowledge of how the proportion of each specific fiber type is regulated in muscle during aging could be considered the primary step for the development of effective strategies for preventing or treating sarcopenia.

The failure of the regeneration of sarcopenic muscle is a major cause of physical incapacitation in the elderly. In addition, there is now a large body of evidence that both sarcopenia and frailty are closely related to the decline of sex hormones that occurs with aging (review in Morley and Malmstrom, 2013). The ability of skeletal muscle tissue to respond to physiological demands and injuries depends on a small population of skeletal muscle stem cells, named as satellite cells (Allen et al., 1999, Hawke and Garry, 2001). For this reason, this review focuses on the potential impact that the estrogen- and testosterone-regulation of satellite cell function has in aged skeletal muscle.

Section snippets

Satellite cells

As it was mentioned, adult skeletal muscle increases its size and shows a remarkable capacity to adapt to trauma and injury. However, myonuclei in skeletal muscle are postmitotic and cannot replicate. Therefore, any increase in myonuclear number required for growth or repair of damaged muscle depends on satellite cells, a pool of myogenic precursor cells. This distinct population of mononucleated cells (Campion, 1984, Grounds et al., 2002) was first described by Mauro (1961). They owe their

Conclusion

Overall, survival radically increased as a result of advances in medicine. Consequently, we are looking at a rising percentage of an aging population. It is well known that sarcopenia increases linearly with aging. Since people are living longer, understanding the molecular mechanisms underlying sarcopenia is critical to the development of therapeutic and preventive strategies to decrease sarcopenia associated poor life quality in the elderly. Since the discovery of skeletal muscle satellite

Acknowledgments

The literary work associated with this article was funded by the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), the Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT) and the Universidad Nacional Del Sur of Argentina.

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