Muscle Protein Synthesis In Response Research Articles

Targeting the Gut Microbiota to Improve Dietary Protein Efficacy to Mitigate Sarcopenia.

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.

Short-term high-fat diet induces muscle fiber type-selective anabolic resistance to resistance exercise.

Chronic obesity and insulin resistance are considered to inhibit contraction-induced muscle hypertrophy, through impairment of mammalian target of rapamycin complex 1 (mTORC1) and muscle protein synthesis (MPS). A high-fat diet is known to rapidly induce obesity and insulin resistance within a month. However, the influence of a short-term high-fat diet on the response of mTORC1 activation and MPS to acute resistance exercise (RE) is unclear. Thus the purpose of this study was to investigate the effect of a short-term high-fat diet on the response of mTORC1 activation and MPS to acute RE. Male Sprague-Dawley rats were randomly assigned to groups and fed a normal diet, high-fat diet, or pair feed for 4 wk. After dietary habituation, acute RE was performed on the gastrocnemius muscle via percutaneous electrical stimulation. The results showed that 4 wk of a high fat-diet induced intramuscular lipid accumulation and insulin resistance, without affecting basal mTORC1 activity or MPS. The response of RE-induced mTORC1 activation and MPS was not altered by a high-fat diet. On the other hand, analysis of each fiber type demonstrated that response of MPS to an acute RE was disappeared specifically in type I and IIa fiber. These results indicate that a short-term high-fat diet causes anabolic resistance to acute RE, depending on the fiber type.NEW & NOTEWORTHY A high-fat diet is known to rapidly induce obesity, insulin resistance, and anabolic resistance to nutrition within a month. However, the influence of a short-term high-fat diet on the response of muscle protein synthesis to acute resistance exercise is unclear. We observed that a short-term high-fat diet causes obesity, insulin resistance, intramuscular lipid droplet accumulation, and anabolic resistance to resistance exercise specifically in type I and IIa fibers.

Singapore multidisciplinary consensus recommendations on muscle health in older adults: assessment and multimodal targeted intervention across the continuum of care

BackgroundThe rapidly aging societies worldwide and in Singapore present a unique challenge, requiring an integrated multidisciplinary approach to address high-value targets such as muscle health. We propose pragmatic evidence-based multidisciplinary consensus recommendations for the assessment and multi-modal management of muscle health in older adults (≥65 years) across the continuum of care.MethodsThe recommendations are derived from an in-depth review of published literature by a multidisciplinary working group with clinical experience in the care of the older population in both acute and community settings.ResultsThe panel recommends screening for muscle impairment using the SARC-F questionnaire, followed by assessment for low muscle strength (handgrip strength or 5-times chair stand test ≥10 s as a surrogate for lower limb strength) to diagnose possible/probable sarcopenia. For uncomplicated cases, lifestyle modifications in exercise and diet can be initiated in the community setting without further assessment. Where indicated, individuals diagnosed with possible/probable sarcopenia should undergo further assessment.Diagnosis of sarcopenia should be based on low muscle strength and low muscle mass (bioimpedance analysis, dual-energy X-ray absorptiometry or calf circumference as a surrogate). The severity of sarcopenia should be determined by assessment of physical performance (gait speed or 5-times chair stand test ≥12 s as a surrogate for gait speed). To treat sarcopenia, we recommend a combination of progressive resistance-based exercise training and optimization of nutritional intake (energy, protein and functional ingredients). High quality protein in sufficient quantity, to overcome anabolic resistance in older adults, and distributed throughout the day to enable maximum muscle protein synthesis, is essential. The addition of resistance-based exercise training is synergistic in improving the sensitivity of muscle protein synthesis response to the provision of amino acids and reducing anabolic resistance. An expected dose-response relationship between the intensity of resistance-based training, lean mass and muscle strength is described.ConclusionsReviewed and endorsed by the Society of Rehabilitation Medicine Singapore and the Singapore Nutrition and Dietetics Association, these multidisciplinary consensus recommendations can provide guidance in the formulation of comprehensive and pragmatic management plans to improve muscle health in older adults in Singapore and Asia.

Dose-Dependent Effects of Protein Ingestion and Resistance Exercise on Muscle Protein Synthesis in Aging Adults: A Literature Review

Introduction: Sarcopenia can lead to physical disability and lower quality of life, but increasing muscle protein synthesis in older adults may reduce its effects. Dose-response curves may be used to determine the optimal protein dose in rested and exercised muscle to elicit maximal muscle protein synthesis. Methods: A literature review was conducted to explore and summarize the findings on the following topics: the mechanisms of muscle protein synthesis, anabolic resistance, and the dose-responses of muscle protein synthesis to anabolic stimuli in both younger and older individuals. Results: Reduced phosphorylation in downstream targets of the mammalian target of rapamycin complex 1 pathway is characteristic of muscle protein synthesis in older muscle. Compared to younger muscle, older muscle can elicit a similar maximal muscle protein synthesis response, but is less sensitive to lower doses of protein ingestion. With ingestion of 40g of whey protein, the fractional synthetic rate in older muscle is similar to that of younger muscle with 20g of whey protein ingestion. Marked increases in amino acid oxidation are also observed. Discussion: Anabolic resistance can be biochemically explained by reduced phosphorylation in the mammalian target of rapamycin complex 1 pathway. Due to this phenomenon, older individuals require greater anabolic stimuli to achieve maximal muscle protein synthesis. However, the most effective protein dose for maximal muscle protein synthesis in older muscle is not well-established. Conclusion: The muscle protein synthesis dose-response curve for older individuals reveals blunted responses to stimuli due to anabolic resistance. Further research is warranted to determine the optimal protein dose for maximal muscle protein synthesis in older adults.

Understanding the effects of nutrition and post-exercise nutrition on skeletal muscle protein turnover: Insights from stable isotope studies

Understanding the effects of nutrition and post-exercise nutrition on skeletal muscle protein turnover: Insights from stable isotope studies

A collagen hydrolysate/milk protein-blend stimulates muscle anabolism equivalently to an isoenergetic milk protein-blend containing a greater quantity of essential amino acids in older men

SummaryBackground & aimsNutritional composition is key for skeletal muscle maintenance into older age. Yet the acute effects of collagen protein blended with other protein sources, in relation to skeletal muscle anabolism, are ill-defined. We investigated human muscle protein synthesis (MPS) responses to a 20 g blend of collagen protein hydrolysate + milk protein (CP+MP, 125 ml) oral nutritional supplement (ONS) vs. 20 g non-blended milk protein source (MP, 200 ml) ONS, in older adults.MethodsHealthy older men (N = 8, 71±1 y, BMI: 27±1 kg·m−2) underwent a randomized trial of 20 g protein, from either a CP+MP blend (Fresubin®3.2 kcal DRINK), or a kcal-matched (higher in essential amino acids (EAA) ONS of MP alone. Vastus lateralis (VL) MPS and plasma AA were determined using stable isotope-tracer mass spectrometry; anabolic signaling was quantified via immuno-blotting in VL biopsies taken at baseline and 2/4 h after ONS feeding. Plasma insulin was measured via enzyme-linked immunosorbent assay (ELISA). Measures were taken at rest, after the feed (FED) and after the feed + exercise (FED-EX) conditions (unilateral leg exercise, 6 × 8, 75% 1-RM).ResultsMP resulted in a greater increase in plasma leucine (MP mean: 152 ± 6 μM, CP+MP mean: 113 ± 4 μM (Feed P < 0.001) and EAA (MP mean: 917 ± 25 μM, CP+MP mean: 786 ± 15 μM (Feed P < 0.01) than CP+MP. CP + MP increased plasma glycine (peak 385 ± 57 μM (P < 0.05)), proline (peak 323 ± 29 μM (P < 0.01)) and non-essential amino acids (NEAA) (peak 1621 ± 107 μM (P < 0.01)) with MP showing no increase. Plasma insulin increased in both trials (CP+MP: 58 ± 10 mU/mL (P < 0.01), MP: 42 ± 6 mU/mL (P < 0.01), with peak insulin greater with CP+MP vs. MP (P < 0.01). MPS demonstrated equivalent increases in response to CP+MP and MP under both FED (MP: 0.039 ± 0.005%/h to 0.081 ± 0.014%/h (P < 0.05), CP+MP: 0.042 ± 0.004%/h to 0.085 ± 0.007%/h (P < 0.05)) and FED-EX (MP: 0.039 ± 0.005%/h to 0.093 ± 0.013%/h (P < 0.01), CP+MP: 0.042 ± 0.004%/h to 0.105 ± 0.015%/h, (P < 0.01)) conditions. FED muscle p-mTOR fold-change from baseline increased to a greater extent with CP+MP vs. MP (P < 0.05), whilst FED-EX muscle p-eEF2 fold-change from baseline decreased to a greater extent with CP+MP vs. MP (P < 0.05); otherwise anabolic signaling responses were indistinguishable.ConclusionFresubin®3.2 kcal DRINK, which contains a 20 g mixed blend of CP+MP, resulted in equivalent MPS responses to MP alone. Fresubin® 3.2 Kcal DRINK may provide a suitable alternative to MP for use in older adults and a convenient way to supplement calories and protein to improve patient adherence and mitigate muscle mass loss.

Habitual protein intake appears to modulate postprandial muscle protein synthesis responses to feeding in youth but not in older age

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Dietary protein, exercise, ageing and physical inactivity: interactive influences on skeletal muscle proteostasis.

Dietary protein is a pre-requisite for the maintenance of skeletal muscle mass; stimulating increases in muscle protein synthesis (MPS), via essential amino acids (EAA), and attenuating muscle protein breakdown, via insulin. Muscles are receptive to the anabolic effects of dietary protein, and in particular the EAA leucine, for only a short period (i.e. about 2-3 h) in the rested state. Thereafter, MPS exhibits tachyphylaxis despite continued EAA availability and sustained mechanistic target of rapamycin complex 1 signalling. Other notable characteristics of this 'muscle full' phenomenon include: (i) it cannot be overcome by proximal intake of additional nutrient signals/substrates regulating MPS; meaning a refractory period exists before a next stimulation is possible, (ii) it is refractory to pharmacological/nutraceutical enhancement of muscle blood flow and thus is not induced by muscle hypo-perfusion, (iii) it manifests independently of whether protein intake occurs in a bolus or intermittent feeding pattern, and (iv) it does not appear to be dependent on protein dose per se. Instead, the main factor associated with altering muscle full is physical activity. For instance, when coupled to protein intake, resistance exercise delays the muscle full set-point to permit additional use of available EAA for MPS to promote muscle remodelling/growth. In contrast, ageing is associated with blunted MPS responses to protein/exercise (anabolic resistance), while physical inactivity (e.g. immobilisation) induces a premature muscle full, promoting muscle atrophy. It is crucial that in catabolic scenarios, anabolic strategies are sought to mitigate muscle decline. This review highlights regulatory protein turnover interactions by dietary protein, exercise, ageing and physical inactivity.

Rapamycin and mTORC2 inhibition synergistically reduce contraction-stimulated muscle protein synthesis.

Muscle contractions increase protein synthesis in a mechanistic target of rapamycin (mTOR)-dependent manner, yet it is unclear which/how mTOR complexes regulate muscle protein synthesis. We investigated the requirement of mTOR Complex 2 (mTORC2) in contraction-stimulated muscle protein synthesis. mTORC2 inhibition by muscle-specific Rictor knockout (Rictor mKO) did not prevent contraction-induced muscle protein synthesis. Rapamycin prevented contraction-induced muscle protein synthesis in Rictor mKO but not wild-type mice. Protein synthesis increases following muscle contractions. Previous studies have shown that inhibition of the mechanistic target of rapamycin complex 1 (mTORC1) suppresses the early but not late muscle protein synthesis response, while inhibition of both mTORC1 and mTORC2 abolishes the two effects. Therefore, we hypothesized that mTORC2 regulates muscle protein synthesis following muscle contractions. To test this, we investigated the effect of mTORC2 inhibition by mouse muscle-specific Rictor knockout (Rictor mKO) on muscle protein synthesis 3h after contraction. The right gastrocnemius muscles of Rictor mKO and wild-type (WT) mice were isometrically contracted using percutaneous electrical stimulation, while the left gastrocnemius muscles served as controls. Vehicle or the mTORC1 inhibitor rapamycin (1.5mg/kg) was injected intraperitoneally 1h before contraction. Treatment of WT mice with rapamycin and Rictor mKO lowered protein synthesis in general, but the response to contractions was intact 3h after contractions in both conditions. Rapamycin treatment in Rictor mKO mice prevented contraction-stimulated muscle protein synthesis. Notably, signalling traditionally associated with mTORC1 was increased by muscle contractions despite rapamycin treatment. In rapamycin-treated Rictor mKO mice, the same mTORC1 signalling was blocked following contractions. Our results indicate that although neither rapamycin-sensitive mTOR/mTORC1 nor mTORC2 is necessary for contraction-induced muscle protein synthesis, combined inhibition of rapamycin-sensitive mTOR/mTORC1 and mTORC2 synergistically inhibits contraction-induced muscle protein synthesis.

Dietary protein considerations for muscle protein synthesis and muscle mass preservation in older adults.

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.

Response of Resistance Exercise-Induced Muscle Protein Synthesis and Skeletal Muscle Hypertrophy Are Not Enhanced After Disuse Muscle Atrophy in Rat.

Skeletal muscle disuse rapidly decreases muscle mass. Resistance training (RT) is believed as the most effective way to gain muscle mass via an increase in mTORC1 activity and muscle protein synthesis (MPS). However, it remains unclear whether muscle atrophy by disuse alters the mTORC1 activation and MPS response to an acute resistance exercise (RE) and chronic RT–mediated skeletal muscle hypertrophy. This study investigated the influence of disuse muscle atrophy on the response of mTORC1 activation and MPS to an acute RE. We also evaluated whether disuse muscle atrophy affects the response of RT-induced muscle mass gain. Thirty male Sprague-Dawley rats were randomly divided into control (CON) or hindlimb suspension (HS) groups. A 14-day HS via the tail was used as the model for gastrocnemius muscle disuse in the HS group. Unilateral lower limb muscle contraction using by percutaneous electrical stimulation was used to mimic the stimuli of RE. Ten bouts of RE were performed in 3-week as chronic RT. Our results showed that MPS and mTORC1 activity was unchanged after HS at basal state. However, the ribosomal RNA (rRNA) level was reduced in HS rats compared to that in CON rats at basal state. MPS and rRNA increased in both HS and CON rats in response to acute RE to the same extent. However, the level of mTORC1 activation in response to an acute RE was significantly higher in HS than that in the CON group at 12 h after exercise, even though no difference was observed at 3 h after exercise. The 10-bout RT significantly increased gastrocnemius muscle mass in both CON and HS rats. The response of muscle hypertrophy did not differ between the groups. Therefore, MPS in response to acute RE and muscle hypertrophy in response to chronic RT were unaltered after disuse muscle atrophy.

Binge drinking effects on markers of skeletal muscle protein synthesis and degradation

Rates of binge drinking in the United States and around the world are increasing despite much data on the detrimental effects associated with this behavior. The deleterious effects of alcohol on brain, liver, and cardiac muscle have been well characterized, but there is still a gap in our understanding of the reduction in the net protein balance in skeletal muscle. Prior work has demonstrated dysregulation in muscle protein synthesis in response to chronic alcohol exposure; however, pathways involved in protein breakdown have been largely unstudied, and studies have been limited to work almost exclusively in males. The aim of the current study was to investigate the effects of binge drinking on markers of muscle protein synthesis and degradation, and to examine the role of exercise in this context. 36 female C57BL/6 mice (7‐weeks of age) were randomized to the following conditions: half of the mice were allowed access to a running wheel for 2.5 hours/day for 5 weeks (EX) and half remained sedentary (SED). During the final week, half of the mice from each condition underwent a binge drinking protocol, in which mice were allowed restricted alcohol access for 2 hours for 4 consecutive days and on the fifth day allowed to drink ad libitum for 4 hours. This experimental paradigm resulted in the following four groups: SED water, SED alcohol, EX water, and EX alcohol. Gastrocnemius gene expression of the muscle enriched ubiquitin ligases MuRF1 and MAFbx, was assessed via qPCR. Phosphorylation of p70S6K was examined by Western blot as an indicator of anabolic signaling. There were no differences in food intake or body weight among groups. MuRF1 was significantly decreased with exercise (p = 0.03), but unaffected by alcohol. There was a significant interaction between alcohol and exercise (p = 0.04), and a main effect of exercise (p &lt; 0.001) on MuRF1. In sedentary mice, alcohol tended to increase MAFbx mRNA (p=0.07); whereas EX alcohol mice had reduced MAFbx compared to SED alcohol (p &lt; 0.001). There was a tendency of exercise to increase phosphorylation of p70S6k (p = 0.065). Our results suggest this model of binge drinking may be useful for determining the effects of binge drinking on the skeletal muscle protein balance, and alcohol may promote expression of atrogenes. In addition, daily exercise could mitigate the dysregulation in skeletal muscle homeostasis caused by alcohol.

Habitual high-protein diet does not influence muscle protein synthesis in response to acute resistance exercise in rats.

Resistance training combined with consumption of a high-protein diet (HPD) is typically recommended to increase muscle mass, as both acute resistance exercise (RE) and dietary protein intake stimulate mechanistic target of rapamycin complex 1 (mTORC1) and muscle protein synthesis (MPS). However, the effect of chronic HPD consumption on MPS response to an acute RE remains to be determined. Male Sprague-Dawley rats aged 10 wk were fed HPD (50 kcal % protein, for 4 wk) or normal protein diet (NPD; 20 kcal % protein). After the 4-wk dietary intervention, the rats were fasted overnight and the right gastrocnemius muscle was subjected to percutaneous electrical stimulation to mimic acute RE, whereas the left gastrocnemius muscle served as control. The rats were sacrificed 6 h after exercise and the tissues were sampled immediately. The HPD group showed significantly lower fat mass and higher skeletal muscle mass than the NPD group without affecting body weight. Resting mTORC1 activity did not differ between the groups. Additionally, resting MPS was also unchanged after HPD. Acute RE significantly increased mTORC1 activity and MPS in both groups. However, differences in diet did not influence the response of mTORC1 activation to acute RE. Furthermore, HPD did not affect the response of MPS to acute RE. The present results suggested that although 4 wk of HPD reduces body fat and increases skeletal muscle mass, it does not affect muscle protein synthesis at basal state, and in response to acute RE.

Whey protein but not collagen peptides stimulate acute and longer-term muscle protein synthesis with and without resistance exercise in healthy older women: a randomized controlled trial

Aging appears to attenuate the response of skeletal muscle protein synthesis (MPS) to anabolic stimuli such as protein ingestion (and the ensuing hyperaminoacidemia) and resistance exercise (RE). The purpose of this study was to determine the effects of protein quality on feeding- and feeding plus RE-induced increases of acute and longer-term MPS after ingestion of whey protein (WP) and collagen protein (CP). In a double-blind parallel-group design, 22 healthy older women (mean±SD age: 69±3 y, n=11/group) were randomly assigned to consume a 30-gsupplement of either WP or CP twice daily for 6 d. Participants performed unilateral RE twice during the 6-d period to determine the acute (via [13C6]-phenylalanine infusion) and longer-term (ingestion of deuterated water) MPS responses, the primary outcome measures. Acutely, WP increased MPS by a mean±SD 0.017±0.008%/h in the feeding-only leg (Rest) and 0.032±0.012%/h in the feeding plus exercise leg (Exercise) (both P<0.01), whereas CP increased MPS only in Exercise (0.012±0.013%/h) (P<0.01) and MPS was greater in WP than CP in both the Rest and Exercise legs (P=0.02). Longer-term MPS increased by 0.063±0.059%/d in Rest and 0.173±0.104%/d in Exercise (P<0.0001) with WP; however, MPS was not significantly elevated above baseline in Rest (0.011±0.042%/d) or Exercise (0.020±0.034%/d) with CP. Longer-term MPS was greater in WP than in CP in both Rest and Exercise (P<0.001). Supplementation with WP elicited greater increases in both acute and longer-term MPS than CP supplementation, which is suggestive that WP is a more effective supplement to support skeletal muscle retention in older women than CP.This trial was registered at clinicaltrials.gov as NCT03281434.

Molecular regulation of human skeletal muscle protein synthesis in response to exercise and nutrients: a compass for overcoming age-related anabolic resistance.

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.

The Role of the Anabolic Properties of Plant- versus Animal-Based Protein Sources in Supporting Muscle Mass Maintenance: A Critical Review.

Plant-sourced proteins offer environmental and health benefits, and research increasingly includes them in study formulas. However, plant-based proteins have less of an anabolic effect than animal proteins due to their lower digestibility, lower essential amino acid content (especially leucine), and deficiency in other essential amino acids, such as sulfur amino acids or lysine. Thus, plant amino acids are directed toward oxidation rather than used for muscle protein synthesis. In this review, we evaluate the ability of plant- versus animal-based proteins to help maintain skeletal muscle mass in healthy and especially older people and examine different nutritional strategies for improving the anabolic properties of plant-based proteins. Among these strategies, increasing protein intake has led to a positive acute postprandial muscle protein synthesis response and even positive long-term improvement in lean mass. Increasing the quality of protein intake by improving amino acid composition could also compensate for the lower anabolic potential of plant-based proteins. We evaluated and discussed four nutritional strategies for improving the amino acid composition of plant-based proteins: fortifying plant-based proteins with specific essential amino acids, selective breeding, blending several plant protein sources, and blending plant with animal-based protein sources. These nutritional approaches need to be profoundly examined in older individuals in order to optimize protein intake for this population who require a high-quality food protein intake to mitigate age-related muscle loss.

Long-chain n-3 fatty acids as an essential link between musculoskeletal and cardio-metabolic health in older adults.

This narrative review aims to critically evaluate scientific evidence exploring the therapeutic role(s) of long-chain n-3 PUFA in the context of ageing, and specifically, sarcopenia. We highlight that beyond impairments in physical function and a lack of independence, the age-related decline in muscle mass has ramifications for cardio-metabolic health. Specifically, skeletal muscle is crucial in regulating blood glucose homeostasis (and by extension reducing type 2 diabetes mellitus risk) and providing gluconeogenic precursors that are critical for survival during muscle wasting conditions (i.e. AIDS). Recent interest in the potential anabolic action of n-3 PUFA is based on findings from experimental studies that measured acute changes in the stimulation of muscle protein synthesis (MPS) and/or chronic changes in muscle mass and strength in response to fish oil-derived n-3 PUFA supplementation. Key findings include a potentiated response of MPS to amino acid provision or resistance-based exercise with n-3 PUFA in healthy older adults that extrapolated to longer-term changes in muscle mass and strength. The key mechanism(s) underpinning this enhanced response of MPS remains to be fully elucidated, but is likely driven by the incorporation of exogenous n-3 PUFA into the muscle phospholipid membrane and subsequent up-regulation of cell signalling proteins known to control MPS. In conclusion, multiple lines of evidence suggest that dietary n-3 PUFA provide an essential link between musculoskeletal and cardio-metabolic health in older adults. Given that western diets are typically meagre in n-3 PUFA content, nutritional recommendations for maintaining muscle health with advancing age should place greater emphasis on dietary n-3 PUFA intake.

Aerobic Plus Resistance Exercise in Obese Older Adults Improves Muscle Protein Synthesis and Preserves Myocellular Quality Despite Weight Loss

Anabolic resistance and impaired myocellular quality contribute to age-related sarcopenia, which exacerbates with obesity. Diet-induced muscle mass loss is attenuated by resistance or aerobic plus resistance exercise compared to aerobic exercise in obese elderly. We assessed chronic effects of weight loss plus different exercise modalities on muscle protein synthesis response to feeding and myocellular quality. Obese older adults were randomized to a weight-management program plus aerobic, resistance, or combined aerobic and resistance exercise or to control. Participants underwent vastus lateralis biopsies at baseline and 6months. Muscle protein synthesis rate increased more in resistance and combined than in control. Autophagy mediators' expression decreased more in combined than in aerobic, which experienced a higher increase in inflammation and mitochondrial regulators' expression. In obese elderly, combined aerobic and resistance exercise is superior to either mode independently for improving muscle protein synthesis and myocellular quality, thereby maintaining muscle mass during weight-loss therapy.

The Effect of Changing the Contraction Mode During Resistance Training on mTORC1 Signaling and Muscle Protein Synthesis.

Acute resistance exercise (RE) increases muscle protein synthesis (MPS) via activation of mechanistic target of rapamycin complex (mTORC), and chronic resistance exercise training (RT) results in skeletal muscle hypertrophy. Although MPS in response to RE is blunted over time during RT, no effective restorative strategy has been identified. Since eccentric muscle contraction (EC) has the potential to strongly stimulate mTORC1 activation and MPS, changing the muscle contraction mode to EC might maintain the MPS response to RE during chronic RT. Male rats were randomly divided into RE (1 bout of RE) and RT (13 bouts of RE) groups. Additionally, each group was subdivided into isometric contraction (IC) and EC subgroups. The RE groups performed acute, unilateral RE using IC or EC. The RT groups performed 12 bouts of unilateral RE using IC. For bout 13, the RT-IC subgroup performed a further IC bout, while the RT-EC subgroup changed to EC. All muscle contractions were induced by percutaneous electrical stimulation. Muscle samples were obtained at 6 h post exercise in all groups. After the 1st RE bout, the EC group showed significantly higher p70S6K Thr389 phosphorylation than the IC group. However, the phosphorylation of other mTORC1-associated proteins (4E-BP1 and ribosomal protein S6) and the MPS response did not differ between the contraction modes. After the 13th bout of RE, mTORC1 activation and the MPS response were significantly blunted as compared with the 1st bout of RE. Changing from IC to EC did not improve these responses. In conclusion, changing the contraction mode to EC does not reinvigorate the blunted mTORC1 activation and MPS in response to RE during chronic RT.

A single bout of strenuous exercise overcomes lipid-induced anabolic resistance to protein ingestion in overweight, middle-aged men.

High-circulating lipid availability attenuates protein feeding-induced muscle protein synthesis (MPS). Whether the combined effects of exercise and protein ingestion can rescue this inhibition is unknown. In a parallel-groups design, middle-aged sedentary males (n = 28) matched for fat-free mass and body mass index received a 5-h intravenous infusion of either saline/control (n = 9), 20% intralipid infusion (n = 9), or intralipid with concomitant exercise (n = 10). Two hours into each of these infusions, participants received a primed constant infusion of L-(ring-[13C]6)-phenylalanine. Muscle biopsies were taken immediately after control and lipid infusions, at which time, a 30-g protein beverage was ingested. Further biopsies were taken 2 and 4 h after protein ingestion. Intralipid increased plasma free fatty acid concentrations from ∼0.4-2 mM, resulting in an attenuated MPS response to protein ingestion, which was prevented by exercise. Intralipid resulted in a lower peak aminoacidemia following protein ingestion that was exacerbated by prior exercise, suggesting efficiency of the working skeletal muscle to utilize amino acid substrate to drive the postprandial anabolic response. We conclude that in the face of high-fat availability, exercise preserves the sensitivity of skeletal muscle to the anabolic properties of amino acids.-Smiles, W. J., Churchward-Venne, T. A., van Loon, L. J. C., Hawley, J. A., Camera, D. M. A single bout of strenuous exercise overcomes lipid-induced anabolic resistance to protein ingestion in overweight, middle-aged men.