scholarly journals Age-related deficits in skeletal muscle recovery following disuse are associated with neuromuscular junction instability and ER stress, not impaired protein synthesis

Aging ◽  
2016 ◽  
Vol 8 (1) ◽  
pp. 127-146 ◽  
Author(s):  
Leslie M. Baehr ◽  
Daniel W.D. West ◽  
George Marcotte ◽  
Andrea G. Marshall ◽  
Luis Gustavo De Sousa ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Neuromuscular Junction ◽  
Er Stress ◽  
Muscle Recovery ◽  
Age Related

scholarly journals FABP3-mediated membrane lipid saturation alters fluidity and induces ER stress in skeletal muscle with aging

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Seung-Min Lee ◽  
Seol Hee Lee ◽  
Youngae Jung ◽  
Younglang Lee ◽  
Jong Hyun Yoon ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Er Stress ◽  
Lipid Composition ◽  
Membrane Lipid ◽  
Muscle Recovery ◽  
Membrane Lipid Composition ◽  
And Function ◽  
Muscle Homeostasis

Abstract Sarcopenia is characterized by decreased skeletal muscle mass and function with age. Aged muscles have altered lipid compositions; however, the role and regulation of lipids are unknown. Here we report that FABP3 is upregulated in aged skeletal muscles, disrupting homeostasis via lipid remodeling. Lipidomic analyses reveal that FABP3 overexpression in young muscles alters the membrane lipid composition to that of aged muscle by decreasing polyunsaturated phospholipid acyl chains, while increasing sphingomyelin and lysophosphatidylcholine. FABP3-dependent membrane lipid remodeling causes ER stress via the PERK-eIF2α pathway and inhibits protein synthesis, limiting muscle recovery after immobilization. FABP3 knockdown induces a young-like lipid composition in aged muscles, reduces ER stress, and improves protein synthesis and muscle recovery. Further, FABP3 reduces membrane fluidity and knockdown increases fluidity in vitro, potentially causing ER stress. Therefore, FABP3 drives membrane lipid composition-mediated ER stress to regulate muscle homeostasis during aging and is a valuable target for sarcopenia.

scholarly journals Advances in the Role of Leucine-Sensing in the Regulation of Protein Synthesis in Aging Skeletal Muscle

2021 ◽  
Vol 9 ◽  
Author(s):  
Yan Zhao ◽  
Jason Cholewa ◽  
Huayu Shang ◽  
Yueqin Yang ◽  
Xiaomin Ding ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Therapeutic Potential ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Trna Synthetase ◽  
Limiting Factor ◽  
Anabolic Resistance ◽  
Age Related

Skeletal muscle anabolic resistance (i.e., the decrease in muscle protein synthesis (MPS) in response to anabolic stimuli such as amino acids and exercise) has been identified as a major cause of age-related sarcopenia, to which blunted nutrition-sensing contributes. In recent years, it has been suggested that a leucine sensor may function as a rate-limiting factor in skeletal MPS via small-molecule GTPase. Leucine-sensing and response may therefore have important therapeutic potential in the steady regulation of protein metabolism in aging skeletal muscle. This paper systematically summarizes the three critical processes involved in the leucine-sensing and response process: (1) How the coincidence detector mammalian target of rapamycin complex 1 localizes on the surface of lysosome and how its crucial upstream regulators Rheb and RagB/RagD interact to modulate the leucine response; (2) how complexes such as Ragulator, GATOR, FLCN, and TSC control the nucleotide loading state of Rheb and RagB/RagD to modulate their functional activity; and (3) how the identified leucine sensor leucyl-tRNA synthetase (LARS) and stress response protein 2 (Sestrin2) participate in the leucine-sensing process and the activation of RagB/RagD. Finally, we discuss the potential mechanistic role of exercise and its interactions with leucine-sensing and anabolic responses.

scholarly journals Age-related differences in lean mass, protein synthesis and skeletal muscle markers of proteolysis after bed rest and exercise rehabilitation

2015 ◽  
Vol 593 (18) ◽  
pp. 4259-4273 ◽  
Author(s):  
Ruth E. Tanner ◽  
Lucille B. Brunker ◽  
Jakob Agergaard ◽  
Katherine M. Barrows ◽  
Robert A. Briggs ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Lean Mass ◽  
Bed Rest ◽  
Exercise Rehabilitation ◽  
Age Related ◽  
Rest And Exercise

Aging, exercise, and muscle protein metabolism

2009 ◽  
Vol 106 (6) ◽  
pp. 2040-2048 ◽  
Author(s):  
René Koopman ◽  
Luc J. C. van Loon
Keyword(s):  
Physical Activity ◽  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Food Intake ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
The Elderly ◽  
Age Related

Aging is accompanied by a progressive loss of skeletal muscle mass and strength, leading to the loss of functional capacity and an increased risk of developing chronic metabolic disease. The age-related loss of skeletal muscle mass is attributed to a disruption in the regulation of skeletal muscle protein turnover, resulting in an imbalance between muscle protein synthesis and degradation. As basal (fasting) muscle protein synthesis rates do not seem to differ substantially between the young and elderly, many research groups have started to focus on the muscle protein synthetic response to the main anabolic stimuli, i.e., food intake and physical activity. Recent studies suggest that the muscle protein synthetic response to food intake is blunted in the elderly. The latter is now believed to represent a key factor responsible for the age-related decline in skeletal muscle mass. Physical activity and/or exercise stimulate postexercise muscle protein accretion in both the young and elderly. However, the latter largely depends on the timed administration of amino acids and/or protein before, during, and/or after exercise. Prolonged resistance type exercise training represents an effective therapeutic strategy to augment skeletal muscle mass and improve functional performance in the elderly. The latter shows that the ability of the muscle protein synthetic machinery to respond to anabolic stimuli is preserved up to very old age. Research is warranted to elucidate the interaction between nutrition, exercise, and the skeletal muscle adaptive response. The latter is needed to define more effective strategies that will maximize the therapeutic benefits of lifestyle intervention in the elderly.

scholarly journals Low-Grade Systemic Inflammation Interferes with Anabolic and Catabolic Characteristics of the Aged Human Skeletal Muscle

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Dimitrios Draganidis ◽  
Athanasios Z. Jamurtas ◽  
Niki Chondrogianni ◽  
George Mastorakos ◽  
Tobias Jung ◽  
...  
Keyword(s):  
Older Adults ◽  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Systemic Inflammation ◽  
Human Skeletal Muscle ◽  
Acute Phase Proteins ◽  
Proteasome Activity ◽  
Low Grade ◽  
Age Related ◽  
Hs Crp

Aging is associated with the development of chronic low-grade systemic inflammation (LGSI) characterized by increased circulating levels of proinflammatory cytokines and acute phase proteins such as C-reactive protein (CRP). Collective evidence suggests that elevated levels of inflammatory mediators such as CRP, interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α) are correlated with deteriorated skeletal muscle mass and function, though the molecular footprint of this observation in the aged human skeletal muscle remains obscure. Based on animal models showing impaired protein synthesis and enhanced degradation in response to LGSI, we compared here the response of proteolysis- and protein synthesis-related signaling proteins as well as the satellite cell and amino acid transporter protein content between healthy older adults with increased versus physiological blood hs-CRP levels in the fasted (basal) state and after an anabolic stimulus comprised of acute resistance exercise (RE) and protein feeding. Our main findings indicate that older adults with increased hs-CRP levels demonstrate (i) increased proteasome activity, accompanied by increased protein carbonylation and IKKα/β phosphorylation; (ii) reduced Pax7+ satellite cells; (iii) increased insulin resistance, at the basal state; and (iv) impaired S6 ribosomal protein phosphorylation accompanied by hyperinsulinemia following an acute RE bout combined with protein ingestion. Collectively, these data provide support to the concept that age-related chronic LGSI may upregulate proteasome activity via induction of the NF-κB signaling and protein oxidation and impair the insulin-dependent anabolic potential of human skeletal muscle.

scholarly journals Effects of Arginine and Inflammation on Protein Metabolism in Human Skeletal Muscle Cells (P01-034-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Lauren Varvatos ◽  
Jamie Blum ◽  
Janet Back ◽  
Anna Thalacker-Mercer
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Cells ◽  
Radioactive Isotopes ◽  
Treatment Control ◽  
Additional Increase ◽  
Arginine Uptake ◽  
Age Related ◽  
Human Myotubes ◽  
Human Skeletal Muscle Cells

Abstract Objectives Chronic inflammation is a hallmark of skeletal muscle (SkM) with advancing age and is thought to augment age-related SkM atrophy (sarcopenia). Arginine, a conditionally essential amino acid, is necessary for protein synthesis. Intriguingly, arginine has been identified as being important for attenuating nuclear factor kappa B (NF-κB) activity in non-muscle cells. Our objective was to determine the age-related effects of arginine and inflammation on markers of protein synthesis and breakdown in human myotubes. Methods Muscle progenitor cells (MPCs) were obtained from SkM biopsy tissue of young (YNG, n = 5) and old (OLD, n = 5) women. MPCs were differentiated for 5 days (myotubes) followed by treatment with a pro-inflammatory cytokine, TNFα, for 6 h, 24 h, 48 h, or 96 h. Inflammatory activity and arginine uptake were determined using immunoblotting and radioactive isotopes. Protein synthesis was assessed with puromycin incorporation. MURF1 and MAFBX1 gene expression were used as indicators of proteolysis. Results Prior to TNFα treatment, OLD (vs. YNG) myotubes had greater arginine uptake (P = 0.02), but there were no age-related differences in basal p65 NF-κB activity, puromycin incorporation, or MAFBX1 and MURF1 expression (P > 0.05). Treatment with TNFα induced NF-κB activity in both YNG and OLD myotubes at 6 and 24 h of treatment (P < 0.0001), with no additional increase in activity from 24–96 h. CAT2, an arginine transporter, was transiently induced at 6 h of TNFα treatment (P < 0.01), with no age-related difference in response (P > 0.05). 96 h of TNFα increased arginine uptake in OLD (P < 0.05), but not YNG myotubes (P > 0.05). 6 h TNFα had no effect (P > 0.05), but 96 h of TNFα reduced puromycin incorporation in both YNG and OLD myotubes (P < 0.05). Compared to no treatment control, 96 h TNFα unexpectedly decreased MAFBX1 expression in both YNG and OLD myotubes (P < 0.001). Intriguingly, in the presence of TNFα, arginine increased MURF1 expression in YNG and OLD myotubes compared to no treatment control (P < 0.05). Conclusions Unexpectedly, arginine amplified markers of proteolysis, and did not affect protein synthesis. Future studies will investigate regulatory transcription factors involved in protein breakdown and a crude marker of protein balance (e.g., myotube diameter). Funding Sources President's Council for Cornell Women.

scholarly journals Skeletal Muscle Recovery from Disuse Atrophy: Protein Turnover Signaling and Strategies for Accelerating Muscle Regrowth

2020 ◽  
Vol 21 (21) ◽  
pp. 7940
Author(s):  
Timur M. Mirzoev
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Mass ◽  
Mechanical Loading ◽  
Protein Turnover ◽  
Skeletal Muscle Mass ◽  
Molecular Mechanisms ◽  
Muscle Protein ◽  
Muscle Recovery ◽  
Mechanical Unloading

Skeletal muscle fibers have a unique capacity to adjust their metabolism and phenotype in response to alternations in mechanical loading. Indeed, chronic mechanical loading leads to an increase in skeletal muscle mass, while prolonged mechanical unloading results in a significant decrease in muscle mass (muscle atrophy). The maintenance of skeletal muscle mass is dependent on the balance between rates of muscle protein synthesis and breakdown. While molecular mechanisms regulating protein synthesis during mechanical unloading have been relatively well studied, signaling events implicated in protein turnover during skeletal muscle recovery from unloading are poorly defined. A better understanding of the molecular events that underpin muscle mass recovery following disuse-induced atrophy is of significant importance for both clinical and space medicine. This review focuses on the molecular mechanisms that may be involved in the activation of protein synthesis and subsequent restoration of muscle mass after a period of mechanical unloading. In addition, the efficiency of strategies proposed to improve muscle protein gain during recovery is also discussed.

scholarly journals Dietary protein and exercise training in ageing

2010 ◽  
Vol 70 (1) ◽  
pp. 104-113 ◽  
Author(s):  
René Koopman
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Exercise Training ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Human Subjects ◽  
The Elderly ◽  
Age Related

Ageing is accompanied by a progressive loss of skeletal muscle mass and strength, leading to the loss of functional capacity and an increased risk for developing chronic metabolic diseases such as diabetes. The age-related loss of skeletal muscle mass results from a chronic disruption in the balance between muscle protein synthesis and degradation. As basal muscle protein synthesis rates are likely not different between healthy young and elderly human subjects, it was proposed that muscles from older adults lack the ability to regulate the protein synthetic response to anabolic stimuli, such as food intake and physical activity. Indeed, the dose–response relationship between myofibrillar protein synthesis and the availability of essential amino acids and/or resistance exercise intensity is shifted down and to the right in elderly human subjects. This so-called ‘anabolic resistance’ represents a key factor responsible for the age-related decline in skeletal muscle mass. Interestingly, long-term resistance exercise training is effective as a therapeutic intervention to augment skeletal muscle mass, and improves functional performance in the elderly. The consumption of different types of proteins, i.e. protein hydrolysates, can have different stimulatory effects on muscle protein synthesis in the elderly, which may be due to their higher rate of digestion and absorption. Current research aims to elucidate the interactions between nutrition, exercise and the skeletal muscle adaptive response that will define more effective strategies to maximise the therapeutic benefits of lifestyle interventions in the elderly.

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