scholarly journals Evidence for the Contribution of Gut Microbiota to Age-Related Anabolic Resistance

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 706
Author(s):  
Matthew D. Watson ◽  
Brett L. Cross ◽  
Gregory J. Grosicki
Keyword(s):  
Skeletal Muscle ◽  
Amino Acid ◽  
Gut Microbiota ◽  
Muscle Protein ◽  
Anabolic Resistance ◽  
Amino Acid Availability ◽  
Age Related ◽  
Protein Feeding ◽  
And Function ◽  
Age Related Changes

Globally, people 65 years of age and older are the fastest growing segment of the population. Physiological manifestations of the aging process include undesirable changes in body composition, declines in cardiorespiratory fitness, and reductions in skeletal muscle size and function (i.e., sarcopenia) that are independently associated with mortality. Decrements in muscle protein synthetic responses to anabolic stimuli (i.e., anabolic resistance), such as protein feeding or physical activity, are highly characteristic of the aging skeletal muscle phenotype and play a fundamental role in the development of sarcopenia. A more definitive understanding of the mechanisms underlying this age-associated reduction in anabolic responsiveness will help to guide promyogenic and function promoting therapies. Recent studies have provided evidence in support of a bidirectional gut-muscle axis with implications for aging muscle health. This review will examine how age-related changes in gut microbiota composition may impact anabolic response to protein feeding through adverse changes in protein digestion and amino acid absorption, circulating amino acid availability, anabolic hormone production and responsiveness, and intramuscular anabolic signaling. We conclude by reviewing literature describing lifestyle habits suspected to contribute to age-related changes in the microbiome with the goal of identifying evidence-informed strategies to preserve microbial homeostasis, anabolic sensitivity, and skeletal muscle with advancing age.

scholarly journals Mechanisms Linking the Gut-Muscle Axis With Muscle Protein Metabolism and Anabolic Resistance: Implications for Older Adults at Risk of Sarcopenia

2021 ◽  
Vol 12 ◽  
Author(s):  
Konstantinos Prokopidis ◽  
Edward Chambers ◽  
Mary Ni Lochlainn ◽  
Oliver C. Witard
Keyword(s):  
Older Adults ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Gut Microbiota ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Low Grade ◽  
Anabolic Resistance ◽  
Amino Acid Availability ◽  
Low Grade Inflammation

Aging is associated with a decline in skeletal muscle mass and function—termed sarcopenia—as mediated, in part, by muscle anabolic resistance. This metabolic phenomenon describes the impaired response of muscle protein synthesis (MPS) to the provision of dietary amino acids and practice of resistance-based exercise. Recent observations highlight the gut-muscle axis as a physiological target for combatting anabolic resistance and reducing risk of sarcopenia. Experimental studies, primarily conducted in animal models of aging, suggest a mechanistic link between the gut microbiota and muscle atrophy, mediated via the modulation of systemic amino acid availability and low-grade inflammation that are both physiological factors known to underpin anabolic resistance. Moreover, in vivo and in vitro studies demonstrate the action of specific gut bacteria (Lactobacillus and Bifidobacterium) to increase systemic amino acid availability and elicit an anti-inflammatory response in the intestinal lumen. Prospective lifestyle approaches that target the gut-muscle axis have recently been examined in the context of mitigating sarcopenia risk. These approaches include increasing dietary fiber intake that promotes the growth and development of gut bacteria, thus enhancing the production of short-chain fatty acids (SCFA) (acetate, propionate, and butyrate). Prebiotic/probiotic/symbiotic supplementation also generates SCFA and may mitigate low-grade inflammation in older adults via modulation of the gut microbiota. Preliminary evidence also highlights the role of exercise in increasing the production of SCFA. Accordingly, lifestyle approaches that combine diets rich in fiber and probiotic supplementation with exercise training may serve to produce SCFA and increase microbial diversity, and thus may target the gut-muscle axis in mitigating anabolic resistance in older adults. Future mechanistic studies are warranted to establish the direct physiological action of distinct gut microbiota phenotypes on amino acid utilization and the postprandial stimulation of muscle protein synthesis in older adults.

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.

Postexercise Dietary Protein Strategies to Maximize Skeletal Muscle Repair and Remodeling in Masters Endurance Athletes: A Review

2016 ◽  
Vol 26 (2) ◽  
pp. 168-178 ◽  
Author(s):  
Thomas M. Doering ◽  
Peter R. Reaburn ◽  
Stuart M. Phillips ◽  
David G. Jenkins
Keyword(s):  
Dietary Protein ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Endurance Athletes ◽  
Recovery Rates ◽  
Anabolic Resistance ◽  
Age Related ◽  
Masters Athletes ◽  
Protein Feeding ◽  
Muscle Remodeling

Participation rates of masters athletes in endurance events such as long-distance triathlon and running continue to increase. Given the physical and metabolic demands of endurance training, recovery practices influence the quality of successive training sessions and, consequently, adaptations to training. Research has suggested that, after muscle-damaging endurance exercise, masters athletes experience slower recovery rates in comparison with younger, similarly trained athletes. Given that these discrepancies in recovery rates are not observed after non–muscle-damaging exercise, it is suggested that masters athletes have impairments of the protein remodeling mechanisms within skeletal muscle. The importance of postexercise protein feeding for endurance athletes is increasingly being acknowledged, and its role in creating a positive net muscle protein balance postexercise is well known. The potential benefits of postexercise protein feeding include elevating muscle protein synthesis and satellite cell activity for muscle repair and remodeling, as well as facilitating muscle glycogen resynthesis. Despite extensive investigation into age-related anabolic resistance in sedentary aging populations, little is known about how anabolic resistance affects postexercise muscle protein synthesis and thus muscle remodeling in aging athletes. Despite evidence suggesting that physical training can attenuate but not eliminate age-related anabolic resistance, masters athletes are currently recommended to consume the same postexercise dietary protein dose (approximately 20 g or 0.25 g/kg/meal) as younger athletes. Given the slower recovery rates of masters athletes after muscle-damaging exercise, which may be due to impaired muscle remodeling mechanisms, masters athletes may benefit from higher doses of postexercise dietary protein, with particular attention directed to the leucine content of the postexercise bolus.

scholarly journals Does the muscle protein synthetic response to exercise and amino acid-based nutrition diminish with advancing age? A systematic review

2016 ◽  
Vol 311 (5) ◽  
pp. E803-E817 ◽  
Author(s):  
Brandon J. Shad ◽  
Janice L. Thompson ◽  
Leigh Breen
Keyword(s):  
Systematic Review ◽  
Amino Acid ◽  
Acute Exercise ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Sufficient Evidence ◽  
Older Individuals ◽  
Anabolic Resistance ◽  
Age Related ◽  
Response To Exercise

The precise role of age-related muscle anabolic resistance in the progression of sarcopenia and functional decline in older individuals is unclear. The present aim was to assess whether the muscle protein synthesis (MPS) response to acute exercise (endurance or resistance) and/or amino acid-based nutrition is attenuated in older compared with young individuals. A systematic review was conducted on studies that directly examined the influence of age on the MPS response to exercise and/or amino acid-based nutrition. Each study arm was synthesized and reported as providing sufficient or insufficient “evidence of age-related muscle anabolic resistance”. Subsequently, three models were established to compare age-related differences in the MPS response to 1) exercise alone, 2) amino acid-based nutrition alone, or 3) the combination of exercise and amino acid-based nutrition. Following exercise alone, 8 of the 17 study arms provided sufficient evidence of age-related muscle anabolic resistance, while in response to amino acid-based nutrition alone, 8 of the 21 study arms provided sufficient evidence of age-related muscle anabolic resistance. When exercise and amino acid-based nutrition were combined, only 2 of the 10 study arms provided sufficient evidence of age-related muscle anabolic resistance. Our results highlight that optimization of exercise and amino acid-based nutrition is sufficient to induce a comparable MPS response between young and older individuals. However, the exercise volume completed and/or the amino acid/protein dose and leucine content must exceed a certain threshold to stimulate equivalent MPS rates in young and older adults, below which age-related muscle anabolic resistance may become apparent.

scholarly journals Characterising the muscle anabolic potential of dairy, meat and plant-based protein sources in older adults

2017 ◽  
Vol 77 (1) ◽  
pp. 20-31 ◽  
Author(s):  
Stefan H. M. Gorissen ◽  
Oliver C. Witard
Keyword(s):  
Older Adults ◽  
Skeletal Muscle ◽  
Amino Acid ◽  
Muscle Mass ◽  
Dietary Protein ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Amino Acid Profile ◽  
Protein Sources ◽  
Age Related

The age-related loss of skeletal muscle mass and function is caused, at least in part, by a reduced muscle protein synthetic response to protein ingestion. The magnitude and duration of the postprandial muscle protein synthetic response to ingested protein is dependent on the quantity and quality of the protein consumed. This review characterises the anabolic properties of animal-derived and plant-based dietary protein sources in older adults. While approximately 60 % of dietary protein consumed worldwide is derived from plant sources, plant-based proteins generally exhibit lower digestibility, lower leucine content and deficiencies in certain essential amino acids such as lysine and methionine, which compromise the availability of a complete amino acid profile required for muscle protein synthesis. Based on currently available scientific evidence, animal-derived proteins may be considered more anabolic than plant-based protein sources. However, the production and consumption of animal-derived protein sources is associated with higher greenhouse gas emissions, while plant-based protein sources may be considered more environmentally sustainable. Theoretically, the lower anabolic capacity of plant-based proteins can be compensated for by ingesting a greater dose of protein or by combining various plant-based proteins to provide a more favourable amino acid profile. In addition, leucine co-ingestion can further augment the postprandial muscle protein synthetic response. Finally, prior exercise or n-3 fatty acid supplementation have been shown to sensitise skeletal muscle to the anabolic properties of dietary protein. Applying one or more of these strategies may support the maintenance of muscle mass with ageing when diets rich in plant-based protein are consumed.

scholarly journals Nutrition and microRNAs: Novel Insights to Fight Sarcopenia

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 951
Author(s):  
Alessandra Barbiera ◽  
Laura Pelosi ◽  
Gigliola Sica ◽  
Bianca Maria Scicchitano
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Molecular Mechanisms ◽  
Muscle Protein ◽  
Low Grade ◽  
Protein Homeostasis ◽  
Dietary Interventions ◽  
Physiological Processes ◽  
Age Related ◽  
And Function

Sarcopenia is a progressive age-related loss of skeletal muscle mass and strength, which may result in increased physical frailty and a higher risk of adverse events. Low-grade systemic inflammation, loss of muscle protein homeostasis, mitochondrial dysfunction, and reduced number and function of satellite cells seem to be the key points for the induction of muscle wasting, contributing to the pathophysiological mechanisms of sarcopenia. While a range of genetic, hormonal, and environmental factors has been reported to contribute to the onset of sarcopenia, dietary interventions targeting protein or antioxidant intake may have a positive effect in increasing muscle mass and strength, regulating protein homeostasis, oxidative reaction, and cell autophagy, thus providing a cellular lifespan extension. MicroRNAs (miRNAs) are endogenous small non-coding RNAs, which control gene expression in different tissues. In skeletal muscle, a range of miRNAs, named myomiRNAs, are involved in many physiological processes, such as growth, development, and maintenance of muscle mass and function. This review aims to present and to discuss some of the most relevant molecular mechanisms related to the pathophysiological effect of sarcopenia. Besides, we explored the role of nutrition as a possible way to counteract the loss of muscle mass and function associated with ageing, with special attention paid to nutrient-dependent miRNAs regulation. This review will provide important information to better understand sarcopenia and, thus, to facilitate research and therapeutic strategies to counteract the pathophysiological effect of ageing.

Determination of skeletal muscle calpain and calpastatin activities during maturation

1991 ◽  
Vol 261 (6) ◽  
pp. E677-E683 ◽  
Author(s):  
B. R. Ou ◽  
N. E. Forsberg
Keyword(s):  
Skeletal Muscle ◽  
Muscle Protein ◽  
Mrna Level ◽  
Beta Tubulin ◽  
Mrna Concentration ◽  
Beta Actin ◽  
Age Related ◽  
Synthetic Capacity ◽  
Calpain Ii ◽  
Age Related Changes

Our objectives were to characterize events underlying changes in skeletal muscle calpain and calpastatin activities, using maturation as a model. Muscle samples were taken from rabbits of four ages (newborn and 1, 2, and 5 mo old). Concentrations of RNA and protein and activities of calpains I and II and calpastatin were determined. Steady-state concentrations of mRNAs encoding calpain I, calpain II, calpastatin, alpha- and beta-tubulin, and beta-actin were determined using Northern blot analysis. Calpain and calpastatin activities declined markedly between birth and 1 mo of age and remained unchanged thereafter. Several factors accounted for the neonatal losses of calpains and calpastatin. First, muscle protein concentration increased between birth and 1 mo of age and diluted calpain and calpastatin specific activities. Second, there was a marked reduction of muscle RNA concentration between birth and 1 mo of age, which indicates that protein synthetic capacity declined with age. Finally, calpastatin mRNA concentration declined between birth and 1 mo of age and further contributed to developmental losses of calpastatin activity. Calpain I mRNA concentration was unaffected by age, and although calpain II mRNA concentration declined with age, losses were not detected between birth and 1 mo; hence age-related changes in calpain I and II activities are not mediated at the mRNA level. The age-related reductions in calpain II and calpastatin mRNA concentrations resembled age-related changes in alpha- and beta-tubulin and beta-actin mRNA concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Targeting the Gut Microbiota to Improve Dietary Protein Efficacy to Mitigate Sarcopenia

2021 ◽  
Vol 8 ◽  
Author(s):  
Elena de Marco Castro ◽  
Caoileann H. Murphy ◽  
Helen M. Roche
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Gut Microbiota ◽  
Muscle Mass ◽  
Dietary Protein ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Low Grade ◽  
Ageing Population ◽  
Anabolic Resistance

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.

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