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      Muscle protein breakdown is impaired during immobilization compared to during a subsequent retraining period in older men: no effect of anti-inflammatory medication

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          Abstract

          Muscle inactivity reduces muscle protein synthesis (MPS), whereas a subsequent period of rehabilitation resistance training (retraining) increases MPS. However, less is known regarding muscle protein breakdown (MPB) during such conditions. Furthermore, nonsteroidal anti-inflammatory drugs (NSAIDs) may have a dampening effect on MPB during periods of inactivity in older individuals. Thus, we measured the average MPB, by use of the deuterated water methodology, during an immobilization period and a subsequent retraining period in older individuals with and without NSAID treatment. Eighteen men (60–80 years: range) were randomly assigned to ibuprofen (1200 mg/d, Ibu) or placebo (Plc). One lower limb was immobilized in a cast for 2 weeks and retrained for 2 weeks, and 2 × 20 g of whey protein was ingested daily during both periods. Besides MPB, the protein expression of different muscle degradation signaling molecules was investigated. MPB was lower during immobilization compared to retraining ( p < 0.01). NSAID treatment did not affect the MPB rate during immobilization or retraining ( p > 0.05). The protein expression of muscle degradation signaling molecules changed during the study intervention but were unaffected by NSAID treatment. The finding that MPB was lower during immobilization than during retraining indicates that an increased MPB may play an important role in the muscle protein remodeling processes taking place within the initial retraining period. Moreover, NSAID treatment did not significantly influence the MPB rate during 2 weeks of lower limb immobilization or during 2 weeks of subsequent retraining in older individuals.

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          Signaling in muscle atrophy and hypertrophy.

          Muscle performance is influenced by turnover of contractile proteins. Production of new myofibrils and degradation of existing proteins is a delicate balance, which, depending on the condition, can promote muscle growth or loss. Protein synthesis and protein degradation are coordinately regulated by pathways that are influenced by mechanical stress, physical activity, availability of nutrients, and growth factors. Understanding the signaling that regulates muscle mass may provide potential therapeutic targets for the prevention and treatment of muscle wasting in metabolic and neuromuscular diseases.
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            Two weeks of reduced activity decreases leg lean mass and induces "anabolic resistance" of myofibrillar protein synthesis in healthy elderly.

            Alterations in muscle protein metabolism underlie age-related muscle atrophy. During periods of muscle disuse, muscle protein synthesis is blunted, and muscle atrophy occurs in young and old. The impact of a short reduction in physical activity on muscle protein metabolism in older adults is unknown. The aim of this study was to investigate the impact of 14 days of reduced daily steps on fasted and fed-state rates of myofibrillar protein synthesis (MPS) to provide insight into the mechanisms for changes in muscle mass and markers of metabolic health. Before and after 14 days of reduced daily step-count, 10 healthy older adults (age, 72 ± 1 y) underwent measures of insulin sensitivity, muscle strength, physical function, and body composition. Using a primed constant infusion of L-[ring-(13)C6]phenylalanine with serial muscle biopsies, basal, postabsorptive, and postprandial rates of MPS were determined before and after the 14-day intervention. Daily step-count was reduced by approximately 76% to 1413 ± 110 steps per day. Leg fat-free mass was reduced by approximately 3.9% (P < .001). Postabsorptive insulin resistance was increased by approximately 12%, and postprandial insulin sensitivity was reduced by approximately 43% after step reduction (P < .005). Concentrations of TNF-α and C-reactive protein were increased by approximately 12 and 25%, respectively, after step reduction (P < .05). Postprandial rates of MPS were reduced by approximately 26% after the intervention (P = .028), with no difference in postabsorptive rates. The present study demonstrates that 14 days of reduced steps in older adults induces small but measurable reductions in muscle mass that appear to be underpinned by reductions in postprandial MPS and are accompanied by impairments in insulin sensitivity and systemic inflammatory markers and postprandial MPS.
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              Effects of aging on human skeletal muscle after immobilization and retraining.

              Inactivity is a recognized compounding factor in sarcopenia and muscle weakness in old age. However, while the negative effects of unloading on skeletal muscle in young individuals are well elucidated, only little is known about the consequence of immobilization and the regenerative capacity in elderly individuals. Thus the aim of this study was to examine the effect of aging on changes in muscle contractile properties, specific force, and muscle mass characteristics in 9 old (61-74 yr) and 11 young men (21-27 yr) after 2 wk of immobilization and 4 wk of retraining. Both young and old experienced decreases in maximal muscle strength, resting twitch peak torque and twitch rate of force development, quadriceps muscle volume, pennation angle, and specific force after 2 wk of immobilization (P < 0.05). The decline in quadriceps volume and pennation angle was smaller in old compared with young (P < 0.05). In contrast, only old men experienced a decrease in quadriceps activation. After retraining, both young and old regained their initial muscle strength, but old had smaller gains in quadriceps volume compared with young, and pennation angle increased in young only (P < 0.05). The present study is the first to demonstrate that aging alters the neuromuscular response to short-term disuse and recovery in humans. Notably, immobilization had a greater impact on neuronal motor function in old individuals, while young individuals were more affected at the muscle level. In addition, old individuals showed an attenuated response to retraining after immobilization compared with young individuals.
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                Author and article information

                Contributors
                L.Holm@bham.ac.uk
                Journal
                Pflugers Arch
                Pflugers Arch
                Pflugers Archiv
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0031-6768
                1432-2013
                5 February 2020
                5 February 2020
                2020
                : 472
                : 2
                : 281-292
                Affiliations
                [1 ]GRID grid.5254.6, ISNI 0000 0001 0674 042X, Institute of Sports Medicine Copenhagen, Department of Orthopedic Surgery M, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, , University of Copenhagen, ; Copenhagen, Denmark
                [2 ]GRID grid.5254.6, ISNI 0000 0001 0674 042X, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, , University of Copenhagen, ; Copenhagen, Denmark
                [3 ]GRID grid.412285.8, ISNI 0000 0000 8567 2092, Department of Physical Performance, , Norwegian School of Sport Sciences, ; Oslo, Norway
                [4 ]GRID grid.6572.6, ISNI 0000 0004 1936 7486, School of Sport, Exercise and Rehabilitation Sciences, , University of Birmingham, ; Edgbaston, Birmingham, B15 2TT UK
                Author information
                http://orcid.org/0000-0002-4392-9616
                Article
                2353
                10.1007/s00424-020-02353-w
                7035225
                32025814
                c48f5bd3-c56c-423e-aa74-c4bfdf86b145
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 20 August 2019
                : 29 December 2019
                : 26 January 2020
                Funding
                Funded by: Sundhed og Sygdom, Det Frie Forskningsråd (DK)
                Award ID: 09-073587
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100008442, Mejeribrugets ForskningsFond;
                Award ID: NA
                Award Recipient :
                Funded by: Center for Healthy Ageing
                Award ID: NA
                Categories
                Original Article
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2020

                Anatomy & Physiology
                deuterated water,deuterated alanine,muscle degradation,muscle disuse,muscle recovery,nsaid

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