Molecular genetic studies of gene identification for sarcopenia
ABSTRACT Sarcopenia, which is characterized by a progressive decrease of skeletal muscle mass and function with aging, is closely related to several common diseases (such as cardiovascular and airway diseases) and functional impairment/disability. Strong genetic determination has been reported for muscle mass and muscle strength, two most commonly recognized and studied risk phenotypes for sarcopenia, with heritability ranging from 30 to 85% for muscle strength and 45-90% for muscle mass. Sarcopenia has been the subject of increasing genetic research over the past decade. This review is designed to comprehensively summarize the most important and representative molecular genetic studies designed to identify genetic factors associated with sarcopenia. We have methodically reviewed whole-genome linkage studies in humans, quantitative trait loci mapping in animal models, candidate gene association studies, newly reported genome-wide association studies, DNA microarrays and microRNA studies of sarcopenia or related skeletal muscle phenotypes. The major results of each study are tabulated for easy comparison and reference. The findings of representative studies are discussed with respect to their influence on our present understanding of the genetics of sarcopenia. This is a comprehensive review of molecular genetic studies of gene identification for sarcopenia, and an overarching theme for this review is that the currently accumulating results are tentative and occasionally inconsistent and should be interpreted with caution pending further investigation. Consequently, this overview should enhance recognition of the need to validate/replicate the genetic variants underlying sarcopenia in large human cohorts and animal. We believe that further progress in understanding the genetic etiology of sarcopenia will provide valuable insights into important fundamental biological mechanisms underlying muscle physiology that will ultimately lead to improved ability to recognize individuals at risk for developing sarcopenia and our ability to treat this debilitating condition.
- SourceAvailable from: Shy Cian Khor
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- "Researches have been extensively done to identify candidate genes for sarcopenia in different populations . Amongst the genes that have been identified to play important roles in the pathogenesis of sarcopenia are hormone and receptors genes such as vitamin D receptor (VDR) and androgen receptor (AR); growth factors and cytokines genes such as ciliary neurotrophic factor (CNTF), myostatin (MSTN), and insulin-like growth factor 1 (IGF1); structural and metabolic genes such as angiotensin I converting enzyme 1 (ACE) and alpha actinin 3 (ACTN3) . However, these genes are still inconclusive as candidate gene/s that will accelerate the onset of sarcopenia. "
ABSTRACT: Sarcopenia is a geriatric syndrome that is characterized by gradual loss of muscle mass and strength with increasing age. Although the underlying mechanism is still unknown, the contribution of increased oxidative stress in advanced age has been recognized as one of the risk factors of sarcopenia. Thus, eliminating reactive oxygen species (ROS) can be a strategy to combat sarcopenia. In this review, we discuss the potential role of vitamin E in the prevention and treatment of sarcopenia. Vitamin E is a lipid soluble vitamin, with potent antioxidant properties and current evidence suggesting a role in the modulation of signaling pathways. Previous studies have shown its possible beneficial effects on aging and age-related diseases. Although there are evidences suggesting an association between vitamin E and muscle health, they are still inconclusive compared to other more extensively studied chronic diseases such as neurodegenerative diseases and cardiovascular diseases. Therefore, we reviewed the role of vitamin E and its potential protective mechanisms on muscle health based on previous and current in vitro and in vivo studies.07/2014; 2014:16. DOI:10.1155/2014/914853
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- "-dependent L-type calcium channel subunit beta-1; DEP, differentially expressed protein; Fabp3, fatty acid-binding protein 3; Fbxl18, F-box and leucine-rich repeat protein 18; Fbxo22, F-box protein 22; NFAT, nuclear factor of activated T cells; SCX, strong cation exchange; YFP, yellow fluorescent protein balance, frequent falling, and decreased mobility   . A change in the composition of muscles from fast-twitch (type II) to slow-twitch (type I) fibers  and reduced proteins synthesis rates  are observed with age. "
ABSTRACT: Aging is associated with a progressive loss of skeletal muscular function that often leads to progressive disability and loss of independence. Although muscle aging is well documented, the molecular mechanisms of this condition still remain unclear. To gain greater insight into the changes associated with aging of skeletal muscle, we performed quantitative proteomic analyses on young (6-month) and aged (27-month) mouse gastrocnemius muscles using mTRAQ stable isotope mass tags. We identified and quantified a total of 4,585 peptides corresponding to 236 proteins (protein probability > 0.9). Among them, 33 proteins were more than 1.5-fold up-regulated and 20 proteins were more than 1.5-fold down-regulated in aged muscle compared with young muscle. An ontological analysis revealed that differentially expressed proteins belonged to distinct functional groups, including ion homeostasis, energy metabolism, protein turnover, and Ca(2+) signaling. Identified proteins included aralar1, β-enolase, fatty acid-binding protein 3 (Fabp3), 3-hydroxyacyl-CoA dehydrogenase (Hadh), F-box protein 22 (Fbxo22), F-box and leucine-rich repeat protein 18 (Fbxl18), voltage-dependent L-type calcium channel subunit beta-1 (Cacnb1), ryanodine receptor (RyR), and calsequestrin. Ectopic expression of calsequestrin in C2C12 myoblast resulted in decreased activity of nuclear factor of activated T-cells (NFAT) and increased levels of atrogin-1 and MuRF1 E3 ligase, suggesting that these differentially expressed proteins are involved in muscle aging.Proteomics 01/2014; 14(1). DOI:10.1002/pmic.201200497 · 3.81 Impact Factor
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- "Recent surveys indicate that polymorphisms in genes controlling muscle mass in humans and mammals (Bonaldo and Sandri, 2013; Piccirillo et al., 2013), including the genes encoding insulin growth factor 1 (IGF1), myostatin, follistatin and components of the activin receptor protein complex, are linked to increased risk of sarcopenia (Tan et al., 2012). Although it is currently unknown whether these polymorphisms increase or rather decrease the function of these regulators of muscle mass, molecular analysis and interrogation of other data might provide important information. "
ABSTRACT: A characteristic feature of aged humans and other mammals is the debilitating, progressive loss of skeletal muscle function and mass that is known as sarcopenia. Age-related muscle dysfunction occurs to an even greater extent during the relatively short lifespan of the fruit fly Drosophila melanogaster. Studies in model organisms indicate that sarcopenia is driven by a combination of muscle tissue extrinsic and intrinsic factors, and that it fundamentally differs from the rapid atrophy of muscles observed following disuse and fasting. Extrinsic changes in innervation, stem cell function and endocrine regulation of muscle homeostasis contribute to muscle aging. In addition, organelle dysfunction and compromised protein homeostasis are among the primary intrinsic causes. Some of these age-related changes can in turn contribute to the induction of compensatory stress responses that have a protective role during muscle aging. In this Review, we outline how studies in Drosophila and mammalian model organisms can each provide distinct advantages to facilitate the understanding of this complex multifactorial condition and how they can be used to identify suitable therapies.Disease Models and Mechanisms 10/2013; 6(6). DOI:10.1242/dmm.012559 · 4.97 Impact Factor