scholarly journals The Role of the IGF-1 Signaling Cascade in Muscle Protein Synthesis and Anabolic Resistance in Aging Skeletal Muscle

2019 ◽  
Vol 6 ◽  
Author(s):  
Richie D. Barclay ◽  
Nicholas A. Burd ◽  
Christopher Tyler ◽  
Neale A. Tillin ◽  
Richard W. Mackenzie
Author(s):  
Yan Zhao ◽  
Jason Cholewa ◽  
Huayu Shang ◽  
Yueqin Yang ◽  
Xiaomin Ding ◽  
...  

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.


2014 ◽  
Vol 39 (9) ◽  
pp. 987-997 ◽  
Author(s):  
Daniel R. Moore ◽  
Donny M. Camera ◽  
Jose L. Areta ◽  
John A. Hawley

Recovery from the demands of daily training is an essential element of a scientifically based periodized program whose twin goals are to maximize training adaptation and enhance performance. Prolonged endurance training sessions induce substantial metabolic perturbations in skeletal muscle, including the depletion of endogenous fuels and damage/disruption to muscle and body proteins. Therefore, increasing nutrient availability (i.e., carbohydrate and protein) in the post-training recovery period is important to replenish substrate stores and facilitate repair and remodelling of skeletal muscle. It is well accepted that protein ingestion following resistance-based exercise increases rates of skeletal muscle protein synthesis and potentiates gains in muscle mass and strength. To date, however, little attention has focused on the ability of dietary protein to enhance skeletal muscle remodelling and stimulate adaptations that promote an endurance phenotype. The purpose of this review is to critically discuss the results of recent studies that have examined the role of dietary protein for the endurance athlete. Our primary aim is to consider the results from contemporary investigations that have advanced our knowledge of how the manipulation of dietary protein (i.e., amount, type, and timing of ingestion) can facilitate muscle remodelling by promoting muscle protein synthesis. We focus on the role of protein in facilitating optimal recovery from, and promoting adaptations to strenuous endurance-based training.


2018 ◽  
Author(s):  
Brad Jon Schoenfeld ◽  
Bret Contreras

This letter is a response to the paper by Damas et al (2017) titled, “The development of skeletal muscle hypertrophy through resistance training: the role of muscle damage and muscle protein synthesis,” which, in part, endeavored to review the role of exercise-induced muscle damage on muscle hypertrophy. We feel there are a number of issues in interpretation of research and extrapolation that preclude drawing the inference expressed in the paper that muscle damage neither explains nor potentiates increases in muscle hypertrophy. The intent of our letter is not to suggest that a causal role exists between hypertrophy and microinjury. Rather, we hope to provide balance to the evidence presented and offer the opinion that the jury is still very much out as to providing answers on the topic.


2020 ◽  
pp. 1-11 ◽  
Author(s):  
Eunice T. Olaniyan ◽  
Fiona O’Halloran ◽  
Aoife L. McCarthy

Abstract Amino acid bioavailability is critical for muscle protein synthesis (MPS) and preservation of skeletal muscle mass (SMM). Ageing is associated with reduced responsiveness of MPS to essential amino acids (EAA). Further, the older adult population experiences anabolic resistance, leading to increased frailty, functional decline and depleted muscle mass preservation, which facilitates the need for increased protein intake to increase their SMM. This review focuses on the role of proteins in muscle mass preservation and examines the contribution of EAA and protein intake patterns to MPS. Leucine is the most widely studied amino acid for its role as a potent stimulator of MPS, though due to inadequate data little is yet known about the role of other EAA. Reaching a conclusion on the best pattern of protein intake has proven difficult due to conflicting studies. A mixture of animal and plant proteins can contribute to increased MPS and potentially attenuate muscle wasting conditions; however, there is limited research on the biological impact of protein blends in older adults. While there is some evidence to suggest that liquid protein foods with higher than the RDA of protein may be the best strategy for achieving high MPS rates in older adults, clinical trials are warranted to confirm an association between food form and SMM preservation. Further research is warranted before adequate recommendations and strategies for optimising SMM in the elderly population can be proposed.


2021 ◽  
Vol 8 ◽  
Author(s):  
Elena de Marco Castro ◽  
Caoileann H. Murphy ◽  
Helen M. Roche

Sarcopenia is characterised by the presence of diminished skeletal muscle mass and strength. It is relatively common in older adults as ageing is associated with anabolic resistance (a blunted muscle protein synthesis response to dietary protein consumption and resistance exercise). Therefore, interventions to counteract anabolic resistance may benefit sarcopenia prevention and are of utmost importance in the present ageing population. There is growing speculation that the gut microbiota may contribute to sarcopenia, as ageing is also associated with [1) dysbiosis, whereby the gut microbiota becomes less diverse, lacking in healthy butyrate-producing microorganisms and higher in pathogenic bacteria, and [2) loss of epithelial tight junction integrity in the lining of the gut, leading to increased gut permeability and higher metabolic endotoxemia. Animal data suggest that both elements may impact muscle physiology, but human data corroborating the causality of the association between gut microbiota and muscle mass and strength are lacking. Mechanisms wherein the gut microbiota may alter anabolic resistance include an attenuation of gut-derived low-grade inflammation and/or the increased digestibility of protein-containing foods and consequent higher aminoacidemia, both in favour of muscle protein synthesis. This review focuses on the putative links between the gut microbiota and skeletal muscle in the context of sarcopenia. We also address the issue of plant protein digestibility because plant proteins are increasingly important from an environmental sustainability perspective, yet they are less efficient at stimulating muscle protein synthesis than animal proteins.


2019 ◽  
Vol 317 (6) ◽  
pp. C1061-C1078 ◽  
Author(s):  
Nathan Hodson ◽  
Daniel W. D. West ◽  
Andrew Philp ◽  
Nicholas A. Burd ◽  
Daniel R. Moore

Skeletal muscle mass, a strong predictor of longevity and health in humans, is determined by the balance of two cellular processes, muscle protein synthesis (MPS) and muscle protein breakdown. MPS seems to be particularly sensitive to changes in mechanical load and/or nutritional status; therefore, much research has focused on understanding the molecular mechanisms that underpin this cellular process. Furthermore, older individuals display an attenuated MPS response to anabolic stimuli, termed anabolic resistance, which has a negative impact on muscle mass and function, as well as quality of life. Therefore, an understanding of which, if any, molecular mechanisms contribute to anabolic resistance of MPS is of vital importance in formulation of therapeutic interventions for such populations. This review summarizes the current knowledge of the mechanisms that underpin MPS, which are broadly divided into mechanistic target of rapamycin complex 1 (mTORC1)-dependent, mTORC1-independent, and ribosomal biogenesis-related, and describes the evidence that shows how they are regulated by anabolic stimuli (exercise and/or nutrition) in healthy human skeletal muscle. This review also summarizes evidence regarding which of these mechanisms may be implicated in age-related skeletal muscle anabolic resistance and provides recommendations for future avenues of research that can expand our knowledge of this area.


Author(s):  
Mary Ni Lochlainn ◽  
Ruth C. E. Bowyer ◽  
Claire J. Steves

Muscle mass, strength and physical function are known to decline with age. This is associated with the development of geriatric syndromes including sarcopenia and frailty. These conditions are associated with disability, falls, longer hospital stay, higher readmission rates, institutionalisation, osteoporosis, and death. Moreover, they are associated with reduced quality of life, as well as substantial costs to health services around the world. Dietary protein is essential for skeletal muscle function. Older adults have shown evidence of anabolic resistance, where greater amounts of protein are required to stimulate muscle protein synthesis and therefore require higher daily amounts of dietary protein. Research shows that resistance exercise has the most beneficial effect on preserving skeletal muscle. A synergistic effect has been noted when this is combined with dietary protein, yet studies in this area lack consistency. This is due, in part, to the variation that exists within dietary protein, in terms of dose, quality, source, amino acid composition and timing. Research has targeted participants that are replete in dietary protein with negative results. Inconsistent measures of muscle mass, muscle function, physical activity and diet are used. This review attempts to summarise these issues, as well as introduce the possible role of the gut microbiome and its metabolome in this area.


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