Review17β-Estradiol and testosterone in sarcopenia: Role of satellite cells
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.
References (193)
- et al.
Activation of membrane estrogen receptors induce pro-survival kinases
J. Steroid Biochem. Mol. Biol.
(2006) - et al.
Exercise-induced muscle protein leakage in the rat. Effects of hormonal manipulation
J. Neurol. Sci.
(1986) - et al.
Transforming growth factor-β-activated kinase 1 is an essential regulator of myogenic differentiation
J. Biol. Chem.
(2010) - et al.
Cytoplasmic activation of human nuclear genes in stable heterocaryons
Cell
(1983) - et al.
Testosterone inhibits transforming growth factor-β signaling during myogenic differentiation and proliferation of mouse satellite cells: potential role of follistatin in mediating testosterone action
Mol. Cell. Endocrinol.
(2012) The muscle satellite cell—a review
Int. Rev. Cytol.
(1984)- et al.
Impact of ageing on muscle cell regeneration
Ageing Res. Rev.
(2011) - et al.
Atrophy-related ubiquitin ligases, atrogin-1 and MuRF1 are up-regulated in aged rat tibialis anterior muscle
Mech. Ageing Dev.
(2006) - et al.
Effects of sex steroids on expression of genes regulating growth-related mechanisms in rainbow trout (Oncorhynchus mykiss)
Gen. Comp. Endocrinol.
(2015) - et al.
New therapies for Duchenne muscular dystrophy: challenges, prospects and clinical trials
Trends Mol. Med.
(2007)
The depletion of skeletal muscle satellite cells with age is concomitant with reduced capacity of single progenitors to produce reserve progeny
Dev. Biol.
Selective downregulation of ubiquitin conjugation cascade mRNA occurs in the senescent rat soleus muscle
Exp. Gerontol.
Stem cells in postnatal myogenesis: molecular mechanisms of satellite cell quiescence, activation and replenishment
Trends Cell Biol.
Sarcopenia: an undiagnosed condition in older adults. Current consensus definition: prevalence, etiology and consequences. International Working Group on sarcopenia
J. Am. Med. Dir. Assoc.
Nitric oxide regulates the repair of injured skeletal muscle
Nitric Oxide
Enhancement of myogenic and muscle repair capacities of human adipose-derived stem cells with forced expression of MyoD
Mol. Ther.
C2C12 myoblasts release micro-vesicles containing mtDNA and proteins involved in signal transduction
Exp. Cell Res.
Follistatin, an antagonist of activin, is expressed in the Spemann organizer and displays direct neutralizing activity
Cell
Active allies: hormones, stem cells and the niche in adult mammopoiesis
Trends Endocrinol. Metab.
Characterization of the androgen receptor in the skeletal muscle of the rat
Steroids
Biological progression from adult bone marrow to mononucleate muscle stem cell to multinucleate muscle fiber in response to injury
Cell
What is the cause of the aging atrophy? Total number, size and proportion of different fiber types studied in whole vastus lateralis muscle from 15- to 83-year-old men
J. Neurol. Sci.
Modulation of age-induced apoptotic signaling and cellular remodeling by exercise and calorie restriction in skeletal muscle
Free Radic. Biol. Med.
Skeletal muscle apoptosis, sarcopenia and frailty at old age
Exp. Gerontol.
Cellular adaptation contributes to calorie restriction induced preservation of skeletal muscle in aged rhesus monkeys
Exp. Gerontol.
Myonuclear domains in muscle adaptation and disease
Muscle Nerve
Sex-linked variation in creatine kinase release, and its dependence on oestradiol, can be demonstrated in an in-vitro rat skeletal muscle preparation
Acta Physiol. Scan.
Muscle damage revisited: does tamoxifen protect by membrane stabilisation or radical scavenging, rather then via the E2-receptor?
Biochem. Soc. Trans.
Protection against muscle damage exerted by oestrogen: hormonal or antioxidant action?
Biochem. Soc. Trans.
Expression of CD34 and Myf5 defines the majority of quiescent adult skeletal muscle satellite cells
J. Cell Biol.
Age-dependent effects on functional aspects in human satellite cells
Ann. N. Y. Acad. Sci.
Functional testosterone receptors in plasma membrane of T cells
FASEB J.
Testosterone supplementation for aging-associated sarcopenia
J. Gerontol. A Biol. Sci. Med. Sci.
The effects of supraphysiologic doses of testosterone on muscle size and strength in men
New Engl. J. Med.
A replacement dose of testosterone increases fat-free mass and muscle size in hypogonadal men
J. Clin. Endocr. Metab.
Effects of testosterone replacement and resistance exercise on muscle strength, and body composition in human immunodeficiency virus-infected men with weight loss and low testosterone levels
JAMA
Proof of the effect of testosterone on skeletal muscle
J. Endocrinol.
Defining a role for non-satellite stem cells in the regulation of muscle repair following exercise
Front. Physiol.
Proteasome activities in the rectus abdominis muscle of young and older individuals
Biogerontology
Regulatory factors and cell populations involved in skeletal muscle regeneration
J. Cell. Physiol.
No change in skeletal muscle satellite cells in young and aging rat soleus muscle
J. Physiol. Sci.
Single hematopoietic stem cells generate skeletal muscle through myeloid intermediates
Nat. Med.
Imbalance between pSmad3 and Notch induces CDK inhibitors in old muscle stem cells
Nature
Molecular aging and rejuvenation of human muscle stem cells
EMBO Mol. Med.
Cellular mechanisms and local progenitor activation to regulate skeletal muscle mass
J. Muscle Res. Cell Motil.
Aging-related satellite cell differentiation defect occurs prematurely after ski-induced muscle hypertrophy
Am. J. Physiol. Cell Physiol.
Cellular and molecular regulation of muscle regeneration
Physiol. Rev.
Muscle satellite cells and endothelial cells: close neighbors and privileged partners
Mol. Biol. Cell
Notch-mediated restoration of regenerative potential aged muscle
Science
Aging, stem cells and tissue regeneration: lessons from muscle
Cell Cycle
Cited by (51)
Weight gain in midlife women: Understanding drivers and underlying mechanisms
2022, Current Opinion in Endocrine and Metabolic ResearchCitation Excerpt :Many midlife women exhibit reduced muscle mass, low physical performance, dynapenia, pre-sarcopenia, sarcopenia or sarcopenic obesity (i.e., the coexistence of sarcopenia and obesity), with the postmenopausal status being a predictor of all [33–37]. Menopause transition is associated with a decline in estradiol concentrations and unfavorable changes in cortisol, growth hormone, insulin growth factors, visceral adiposity, bone mineral density, muscle mass, and muscle strength [28], predisposing women to sarcopenia, sarcopenic obesity and osteoporosis [32]. As early as 1936, the first study on the heat production of participants of different age-groups, all employees of the Mayo Clinic, was published by Du Bois [38], revealing a linear decline in the BMR between 24 and 64 years.
Autologous mesenchymal stem cells in the treatment of spinal aneurysmal bone cyst
2022, Pathology Research and PracticeSex differences in the response to oxidative and proteolytic stress
2020, Redox Biology