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

scholarly journals Resistance exercise maintains skeletal muscle protein synthesis during bed rest

1997 ◽  
Vol 82 (3) ◽  
pp. 807-810 ◽  
Author(s):  
Arny A. Ferrando ◽  
Kevin D. Tipton ◽  
Marcas M. Bamman ◽  
Robert R. Wolfe
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Resistance Training ◽  
Resistance Exercise ◽  
Lean Body Mass ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Bed Rest ◽  
Skeletal Muscle Protein ◽  
Skeletal Muscle Protein Synthesis

Ferrando, Arny A., Kevin D. Tipton, Marcas M. Bamman, and Robert R. Wolfe. Resistance exercise maintains skeletal muscle protein synthesis during bed rest. J. Appl. Physiol. 82(3): 807–810, 1997.—Spaceflight results in a loss of lean body mass and muscular strength. A ground-based model for microgravity, bed rest, results in a loss of lean body mass due to a decrease in muscle protein synthesis (MPS). Resistance training is suggested as a proposed countermeasure for spaceflight-induced atrophy because it is known to increase both MPS and skeletal muscle strength. We therefore hypothesized that scheduled resistance training throughout bed rest would ameliorate the decrease in MPS. Two groups of healthy volunteers were studied during 14 days of simulated microgravity. One group adhered to strict bed rest (BR; n = 5), whereas a second group engaged in leg resistance exercise every other day throughout bed rest (BREx; n = 6). MPS was determined directly by the incorporation of infusedl-[ ring-13C6]phenylalanine into vastus lateralis protein. After 14 days of bed rest, MPS in the BREx group did not change and was significantly greater than in the BR group. Thus moderate-resistance exercise can counteract the decrease in MPS during bed rest.

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.

Protein Metabolism and Age: Influence of Insulin and Resistance Exercise

2001 ◽  
Vol 11 (s1) ◽  
pp. S150-S163 ◽  
Author(s):  
Peter A. Farrell
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Resistance Exercise ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Mrna Translation ◽  
Bed Rest ◽  
Skeletal Muscle Protein ◽  
Amino Acid Availability ◽  
Effects Of Aging

Skeletal muscle proteins are constantly being synthesized and degraded, and the net balance between synthesis and degradation determines the resultant muscle mass. Biochemical pathways that control protein synthesis are complex, and the following must be considered: gene transcription, mRNA splicing, and transport to the cytoplasm; specific amino acyl-tRNA, messenger (mRNA), ribosomal (rRNA) availability; amino acid availability within the cell; the hormonal milieu; rates of mRNA translation; packaging in vesicles for some types of proteins; and post-translational processing such as glycation and phosphorylation/dephosphorylation. Each of these processes is responsive to the need for greater or lesser production of new proteins, and many states such as sepsis, uncontrolled diabetes, prolonged bed-rest, aging, chronic alcohol treatment, and starvation cause marked reductions in rates of skeletal muscle protein synthesis. In contrast, acute and chronic resistance exercise cause elevations in rates of muscle protein synthesis above rates found in nondiseased rested organisms, which are normally fed. Resistance exercise may be unique in this capacity. This chapter focuses on studies that have used exercise to elucidate mechanisms that explain elevations in rates of protein synthesis. Very few studies have investigated the effects of aging on these mechanisms; however, the literature that is available is reviewed.

scholarly journals The mTORC1 signaling repressors REDD1/2 are rapidly induced and activation of p70S6K1 by leucine is defective in skeletal muscle of an immobilized rat hindlimb

2013 ◽  
Vol 304 (2) ◽  
pp. E229-E236 ◽  
Author(s):  
Andrew R. Kelleher ◽  
Scot R. Kimball ◽  
Michael D. Dennis ◽  
Rudolf J. Schilder ◽  
Leonard S. Jefferson
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Molecular Mechanisms ◽  
Bed Rest ◽  
Disuse Atrophy ◽  
Sprague Dawley ◽  
Ribosomal Protein S6 ◽  
Sprague Dawley Rats ◽  
Mtorc1 Signaling ◽  
Limb Immobilization

Limb immobilization, limb suspension, and bed rest cause substantial loss of skeletal muscle mass, a phenomenon termed disuse atrophy. To acquire new knowledge that will assist in the development of therapeutic strategies for minimizing disuse atrophy, the present study was undertaken with the aim of identifying molecular mechanisms that mediate control of protein synthesis and mechanistic target of rapamycin complex 1 (mTORC1) signaling. Male Sprague-Dawley rats were subjected to unilateral hindlimb immobilization for 1, 2, 3, or 7 days or served as nonimmobilized controls. Following an overnight fast, rats received either saline or l-leucine by oral gavage as a nutrient stimulus. Hindlimb skeletal muscles were extracted 30 min postgavage and analyzed for the rate of protein synthesis, mRNA expression, phosphorylation state of key proteins in the mTORC1 signaling pathway, and mTORC1 signaling repressors. In the basal state, mTORC1 signaling and protein synthesis were repressed within 24 h in the soleus of an immobilized compared with a nonimmobilized hindlimb. These responses were accompanied by a concomitant induction in expression of the mTORC1 repressors regulated in development and DNA damage responses (REDD) 1/2. The nutrient stimulus produced an elevation of similar magnitude in mTORC1 signaling in both the immobilized and nonimmobilized muscle. In contrast, phosphorylation of 70-kDa ribosomal protein S6 kinase 1 (p70S6K1) on Thr229 and Thr389 in response to the nutrient stimulus was severely blunted. Phosphorylation of Thr229 by PDK1 is a prerequisite for phosphorylation of Thr389 by mTORC1, suggesting that signaling through PDK1 is impaired in response to immobilization. In conclusion, the results show an immobilization-induced attenuation of mTORC1 signaling mediated by induction of REDD1/2 and defective p70S6K1 phosphorylation.

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 Short-term bed rest increases TLR4 and IL-6 expression in skeletal muscle of older adults

2013 ◽  
Vol 305 (3) ◽  
pp. R216-R223 ◽  
Author(s):  
Micah J. Drummond ◽  
Kyle L. Timmerman ◽  
Melissa M. Markofski ◽  
Dillon K. Walker ◽  
Jared M. Dickinson ◽  
...  
Keyword(s):  
Older Adults ◽  
Skeletal Muscle ◽  
Inflammatory Cytokines ◽  
Muscle Biopsy ◽  
Lean Mass ◽  
Bed Rest ◽  
Short Term ◽  
Tlr4 Signaling ◽  
Adult Skeletal Muscle ◽  
Healthy Older Adults

Bed rest induces significant loss of leg lean mass in older adults. Systemic and tissue inflammation also accelerates skeletal muscle loss, but it is unknown whether inflammation is associated to inactivity-induced muscle atrophy in healthy older adults. We determined if short-term bed rest increases toll-like receptor 4 (TLR4) signaling and pro-inflammatory markers in older adult skeletal muscle biopsy samples. Six healthy, older adults underwent seven consecutive days of bed rest. Muscle biopsies (vastus lateralis) were taken after an overnight fast before and at the end of bed rest. Serum cytokine expression was measured before and during bed rest. TLR4 signaling and cytokine mRNAs associated with pro- and anti-inflammation and anabolism were measured in muscle biopsy samples using Western blot analysis and qPCR. Participants lost ∼4% leg lean mass with bed rest. We found that after bed rest, muscle levels of TLR4 protein expression and interleukin-6 (IL-6), nuclear factor-κB1, interleukin-10, and 15 mRNA expression were increased after bed rest ( P < 0.05). Additionally, the cytokines interferon-γ, and macrophage inflammatory protein-1β, were elevated in serum samples following bed rest ( P < 0.05). We conclude that short-term bed rest in older adults modestly increased some pro- and anti-inflammatory cytokines in muscle samples while systemic changes in pro-inflammatory cytokines were mostly absent. Upregulation of TLR4 protein content suggests that bed rest in older adults increases the capacity to mount an exaggerated, and perhaps unnecessary, inflammatory response in the presence of specific TLR4 ligands, e.g., during acute illness.

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 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
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