Sarcopenia prevalence using handgrip strength or chair stand performance in adults living with type 2 diabetes mellitus.

BACKGROUND: The updated European Working Group on Sarcopenia in Older People (EWGSOP2) recommends handgrip strength (HGS) and the chair stand test (CST) to assess muscle strength, with the CST being a convenient proxy for lower limb strength. However, adiposity may differentially influence these strength criteria and produce discrepant sarcopenia prevalence. OBJECTIVE: To determine the prevalence of sarcopenia using HGS or the CST, and to investigate the associations between these strength criteria and adiposity in adults with type 2 diabetes mellitus. METHODS: The EWGSOP2 definition was used to assess the prevalence of probable (low muscle strength), confirmed (plus low muscle mass) and severe (plus poor physical performance) sarcopenia. Linear regression models were used to study the association between different measures of muscle strength and adiposity. RESULTS: We used data from 732 adults with type 2 diabetes mellitus (35.7% female, aged 64 ± 8 years, body mass index 30.7 ± 5.0 kg/m2). Using the CST compared with HGS produced a higher prevalence of probable (31.7% vs. 7.1%), confirmed (5.6% vs. 1.6%) and severe (1.0% vs. 0.3%) sarcopenia, with poor agreement between strength criteria to identify probable sarcopenia. CST performance, but not HGS, was significantly associated with all measures of adiposity in unadjusted and adjusted models. CONCLUSIONS: Higher levels of adiposity may impact CST performance, but not HGS, resulting in a higher prevalence of sarcopenia in adults with type 2 diabetes mellitus. Consideration should be paid to the most appropriate measure of muscle function in this population.

Postprandial plasma amino acid and appetite responses with ingestion of a novel salmon-derived protein peptide in healthy young adults.

This study assessed postprandial plasma aminoacidemia, glycemia, insulinemia and appetite responses to ingestion of a novel salmon-derived protein peptide (Salmon PP) compared with milk protein isolate (Milk PI). In a randomised, participant-blind crossover design, eleven healthy adults (M = 5, F = 6; mean ± sd age: 22 ± 3 years; BMI: 24 ± 3 kg/m2) ingested 0·3 g/kg/body mass of Salmon PP or Milk PI. Arterialised blood samples were collected whilst fasted and over a 240-min postprandial period. Appetite sensations were measured via visual analogue scales. An ad libitum buffet-style test meal was administered after each trial. The incremental AUC (iAUC) plasma essential amino acid (EAA) response was similar between Salmon PP and Milk PI. The iAUC plasma leucine response was significantly greater following Milk PI ingestion (P < 0·001), whereas temporal and iAUC plasma total amino acid (P = 0·001), non-essential amino acid (P = 0·002), glycine (P = 0·0025) and hydroxyproline (P < 0·001) responses were greater following Salmon PP ingestion. Plasma insulin increased similarly above post-absorptive values following Salmon PP and Milk PI ingestion, whilst plasma glucose was largely unaltered. Indices of appetite were similarly altered following Salmon PP and Milk PI ingestion, and total energy and macronutrient intake during the ad libitum meal was similar between Salmon PP and Milk PI. The postprandial plasma EAA, glycine, proline and hydroxyproline response to Salmon PP ingestion suggest this novel protein source could support muscle and possibly connective tissue adaptive remodelling, which warrants further investigation, particularly as the plasma leucine response to Salmon PP ingestion was inferior to Milk PI.

Dietary protein recommendations to support healthy muscle ageing in the 21st century and beyond: considerations and future directions.

This review explores the evolution of dietary protein intake requirements and recommendations, with a focus on skeletal muscle remodelling to support healthy ageing based on presentations at the 2023 Nutrition Society summer conference. In this review, we describe the role of dietary protein for metabolic health and ageing muscle, explain the origins of protein and amino acid (AA) requirements and discuss current recommendations for dietary protein intake, which currently sits at about 0⋅8 g/kg/d. We also critique existing (e.g. nitrogen balance) and contemporary (e.g. indicator AA oxidation) methods to determine protein/AA intake requirements and suggest that existing methods may underestimate requirements, with more contemporary assessments indicating protein recommendations may need to be increased to >1⋅0 g/kg/d. One example of evolution in dietary protein guidance is the transition from protein requirements to recommendations. Hence, we discuss the refinement of protein/AA requirements for skeletal muscle maintenance with advanced age beyond simply the dose (e.g. source, type, quality, timing, pattern, nutrient co-ingestion) and explore the efficacy and sustainability of alternative protein sources beyond animal-based proteins to facilitate skeletal muscle remodelling in older age. We conclude that, whilst a growing body of research has demonstrated that animal-free protein sources can effectively stimulate and support muscle remodelling in a manner that is comparable to animal-based proteins, food systems need to sustainably provide a diversity of both plant and animal source foods, not least for their protein content but other vital nutrients. Finally, we propose some priority research directions for the field of protein nutrition and healthy ageing.

A single bout of prior resistance exercise attenuates muscle atrophy and declines in myofibrillar protein synthesis during bed-rest in older men.

Impairments in myofibrillar protein synthesis (MyoPS) during bed rest accelerate skeletal muscle loss in older adults, increasing the risk of adverse secondary health outcomes. We investigated the effect of prior resistance exercise (RE) on MyoPS and muscle morphology during a disuse event in 10 healthy older men (65-80 years). Participants completed a single bout of unilateral leg RE the evening prior to 5 days of in-patient bed-rest. Quadriceps cross-sectional area (CSA) was determined prior to and following bed-rest. Serial muscle biopsies and dual stable isotope tracers were used to determine rates of integrated MyoPS (iMyoPS) over a 7 day habitual 'free-living' phase and the bed-rest phase, and rates of acute postabsorptive and postprandial MyoPS (aMyoPS) at the end of bed rest. Quadriceps CSA at 40%, 60% and 80% of muscle length significantly decreased in exercised (EX) and non-exercised control (CTL) legs with bed-rest. The decline in quadriceps CSA at 40% and 60% of muscle length was attenuated in EX compared with CTL. During bed-rest, iMyoPS rates decreased from habitual values in CTL, but not EX, and were significantly different between legs. Postprandial aMyoPS rates increased above postabsorptive values in EX only. The change in iMyoPS over bed-rest correlated with the change in quadriceps CSA in CTL, but not EX. A single bout of RE attenuated the decline in iMyoPS rates and quadriceps atrophy with 5 days of bed-rest in older men. Further work is required to understand the functional and clinical implications of prior RE in older patient populations. KEY POINTS: Age-related skeletal muscle deterioration, linked to numerous adverse health outcomes, is driven by impairments in muscle protein synthesis that are accelerated during periods of disuse. Resistance exercise can stimulate muscle protein synthesis over several days of recovery and therefore could counteract impairments in this process that occur in the early phase of disuse. In the present study, we demonstrate that the decline in myofibrillar protein synthesis and muscle atrophy over 5 days of bed-rest in older men was attenuated by a single bout of unilateral resistance exercise performed the evening prior to bed-rest. These findings suggest that concise resistance exercise intervention holds the potential to support muscle mass retention in older individuals during short-term disuse, with implications for delaying sarcopenia progression in ageing populations.

A focus on leucine in the nutritional regulation of human skeletal muscle metabolism in ageing, exercise and unloading states.

Muscle protein synthesis (MPS) and muscle protein breakdown (MPB) are influenced through dietary protein intake and physical (in)activity, which it follows, regulate skeletal muscle (SKM) mass across the lifespan. Following consumption of dietary protein, the bio-availability of essential amino acids (EAA), and primarily leucine (LEU), drive a transient increase in MPS with an ensuing refractory period before the next MPS stimulation is possible (due to the "muscle full" state). At the same time, MPB is periodically constrained via reflex insulin actions. Layering exercise on top of protein intake increases the sensitivity of SKM to EAA, therefore extending the muscle full set-point (∼48 h), to permit long-term remodelling (e.g., hypertrophy). In contrast, ageing and physical inactivity are associated with a premature muscle full set-point in response to dietary protein/EAA and contractile activity. Of all the EAA, LEU is the most potent stimulator of the mechanistic target of rapamycin complex 1 (mTORC1)-signalling pathway, with the phosphorylation of mTORC1 substrates increasing ∼3-fold more than with all other EAA. Furthermore, maximal MPS stimulation is also achieved following low doses of LEU-enriched protein/EAA, negating the need for larger protein doses. As a result, LEU supplementation has been of long term interest to maximise muscle anabolism and subsequent net protein accretion, especially when in tandem with resistance exercise. This review highlights current knowledge vis-à-vis the anabolic effects of LEU supplementation in isolation, and in enriched protein/EAA sources (i.e., EAA and/or protein sources with added LEU), in the context of ageing, exercise and unloading states.

Greater myofibrillar protein synthesis following weight-bearing activity in obese old compared with non-obese old and young individuals.

The mechanisms through which obesity impacts age-related muscle mass regulation are unclear. In the present study, rates of integrated myofibrillar protein synthesis (iMyoPS) were measured over 48-h prior-to and following a 45-min treadmill walk in 10 older-obese (O-OB, body fat[%]: 33 ± 3%), 10 older-non-obese (O-NO, 20 ± 3%), and 15 younger-non-obese (Y-NO, 13 ± 5%) individuals. Surface electromyography was used to determine thigh muscle "activation". Quadriceps cross-sectional area (CSA), volume, and intramuscular thigh fat fraction (ITFF) were measured by magnetic resonance imaging. Quadriceps maximal voluntary contraction (MVC) was measured by dynamometry. Quadriceps CSA and volume were greater (muscle volume, Y-NO: 1182 ± 232 cm3; O-NO: 869 ± 155 cm3; O-OB: 881 ± 212 cm3, P < 0.01) and ITFF significantly lower (m. vastus lateralis, Y-NO: 3.0 ± 1.0%; O-NO: 4.0 ± 0.9%; O-OB: 9.1 ± 2.6%, P ≤ 0.03) in Y-NO compared with O-NO and O-OB, with no difference between O-NO and O-OB in quadriceps CSA and volume. ITFF was significantly higher in O-OB compared with O-NO. Relative MVC was lower in O-OB compared with Y-NO and O-NO (Y-NO: 5.5 ± 1.6 n·m/kg-1; O-NO: 3.9 ± 1.0 n·m/kg-1; O-OB: 2.9 ± 1.1 n·m/kg-1, P < 0.0001). Thigh muscle "activation" during the treadmill walk was greater in O-OB compared with Y-NO and O-NO (Y-NO: 30.5 ± 13.5%; O-NO: 35.8 ± 19.7%; O-OB: 68.3 ± 32.3%, P < 0.01). Habitual iMyoPS did not differ between groups, whereas iMyoPS was significantly elevated over 48-h post-walk in O-OB (+ 38.6 ± 1.2%·day-1, P < 0.01) but not Y-NO or O-NO (+ 11.4 ± 1.1%·day-1 and + 17.1 ± 1.1%·day-1, respectively, both P > 0.271). Equivalent muscle mass in O-OB may be explained by the muscle anabolic response to weight-bearing activity, whereas the age-related decline in indices of muscle quality appears to be exacerbated in O-OB and warrants further exploration.

Impaired lower limb muscle mass, quality and function in end stage liver disease: A cross-sectional study.

NEW FINDINGS: What is the central question of this study? To what extent does musculoskeletal impairment occur (i.e., muscle mass, quality and function) in patients with end stage liver disease (ESLD) by comparison to a healthy age/sex-matched control group? What is the main finding and its importance? Muscle mass, quality and function are impaired in patients with ESLD (compared to age/sex matched controls). Importantly, greater impairments were seen in lower limb compared to arm and trunk muscle groups. These findings may suggest that there should be greater consideration of muscle health in functionally relevant lower limb muscle groups. ABSTRACT: Sarcopenia is associated with reduced quality of life and increased mortality in patients with end stage liver disease (ESLD). Historically, sarcopenia identification in ESLD utilised L3 skeletal muscle index (SMI). There are few data on muscle quality and function within lower limb muscle groups with high functional relevance. The aim of this prospective case-control study was to evaluate the quadriceps muscle in patients with ESLD. Muscle mass and quality were evaluated using MRI (quadriceps anatomical cross sectional area (ACSA), quadriceps volume index, L3 SMI, quadriceps intermuscular adipose tissue (IMAT)), mid-arm muscle circumference (MAMC) and ultrasonography (vastus lateralis (VL) thickness and quadriceps ACSA). Muscle strength/function was assessed by handgrip strength, peak quadriceps isokinetic torque and chair rise time. Thirty-nine patients with ESLD (55 years, 61% male, 48% alcoholic related liver disease (ArLD), 71% Child-Pugh B/C) and 18 age/sex-matched healthy control participants (HC) were studied. Quadriceps mass was significantly reduced in ESLD versus HC (-17%), but L3 SMI and MAMC were unchanged. Quadriceps IMAT percentage was increased in ESLD (+103%). Handgrip strength (-15%), peak isokinetic torque (-29%), and chair rise time (+56%) were impaired in ESLD. Ultrasound measures of VL thickness (r = 0.56, r = 0.57, r = 0.42) and quadriceps ACSA (r = 0.98, r = 0.86, r = 0.67) correlated to MRI quadriceps ACSA, quadriceps volume and L3 SMI, respectively. Quadriceps muscle mass, quality, and function were impaired in patients with ESLD, whereas conventional assessments of muscle (L3 SMI and MAMC) highlighted no differences between ESLD and HC. Full evaluation of lower limb muscle health is essential in ESLD in order to accurately assess sarcopenia and target future interventions.

Myofibrillar Protein Synthesis and Acute Intracellular Signaling with Elastic Band Resistance Exercise in Young and Older Men.

PURPOSE: Resistance exercise training (RET) attenuates age-related muscle and strength loss ("sarcopenia"). However, compared with machine-based RET, the efficacy of cost-effective, accessible elastic band RET (EB-RET) for muscle adaptive remodeling lacks supporting mechanistic evidence. METHODS: Eight young (YM; 24 ± 4 yr) and eight older (OM; 68 ± 6 yr) untrained males consumed an oral stable isotope tracer (D 2 O) combined with serial vastus lateralis muscle biopsies to measure integrated myofibrillar protein synthesis (iMyoPS) and regulatory signaling over ~48 h before (habitual) and after an acute bout of EB-RET (6 × 12 repetitions at ~70% of one-repetition maximum). iMyoPS was determined via gas chromatography-pyrolysis-isotope ratio mass spectroscopy and regulatory signaling expression by immunoblot. RESULTS: Habitual iMyoPS did not differ between YM and OM (1.62% ± 0.21% vs 1.43% ± 0.47%·d -1 , respectively, P = 0.128). There was a significant increase in iMyoPS after EB-RET in YM (2.23% ± 0.69%·d -1 , P = 0.02), but not OM (1.75% ± 0.54%·d -1 , P = 0.30). EB-RET increased the phosphorylation of key anabolic signaling proteins similarly in YM and OM at 1 h postexercise, including p-IRS-1 Ser636/639 , p-Akt Ser473 , p-4EBP-1 Thr37/46 , p-P70S6K Thr389 , and p-RPS6 Ser240/244 , whereas p-TSC2 Thr1462 and p-mTOR Ser2448 increased only in YM (all P < 0.05). There were no differences in the expression of amino acid transporters/sensors or proteolytic markers after EB-RET. CONCLUSIONS: iMyoPS was elevated after EB-RET in YM but not OM. However, the increase in acute anabolic signaling with EB-RET was largely similar between groups. In conclusion, the capacity for EB-RET to stimulate iMyoPS may be impaired in older age. Further work may be necessary to optimize prescriptive programming in YM and OM.

Dietary protein requirements and recommendations for healthy older adults: a critical narrative review of the scientific evidence.

Adequate protein intake is essential for the maintenance of whole-body protein mass. Different methodological approaches are used to substantiate the evidence for the current protein recommendations, and it is continuously debated whether older adults require more protein to counteract the age-dependent loss of muscle mass, sarcopenia. Thus, the purpose of this critical narrative review is to outline and discuss differences in the approaches and methodologies assessing the protein requirements and, hence, resulting in controversies in current protein recommendations for healthy older adults. Through a literature search, this narrative review first summarises the historical development of the Food and Agriculture Organization/World Health Organization/United Nations University setting of protein requirements and recommendations for healthy older adults. Hereafter, we describe the various types of studies (epidemiological studies and protein turnover kinetic measurements) and applied methodological approaches founding the basis and the different recommendations with focus on healthy older adults. Finally, we discuss important factors to be considered in future studies to obtain evidence for international agreement on protein requirements and recommendations for healthy older adults. We conclude by proposing future directions to determine 'true' protein requirements and recommendations for healthy older adults.

Improving physiological relevance of cell culture: the possibilities, considerations, and future directions of the ex vivo coculture model.

In vitro models provide an important platform for the investigation of cellular growth and atrophy to inform, or extend mechanistic insights from, logistically challenging in vivo trials. Although these models allow for the identification of candidate mechanistic pathways, many models involve supraphysiological dosages, nonphysiological conditions, or experimental changes relating to individual proteins or receptors, all of which limit translation to human trials. To overcome these drawbacks, the use of ex vivo human plasma and serum has been used in cellular models to investigate changes in myotube hypertrophy, cellular protein synthesis, anabolic and catabolic markers in response to differing age, disease states, and nutrient status. However, there are currently no concurrent guidelines outlining the optimal methodology for this model. This review discusses the key methodological considerations surrounding the use of ex vivo plasma and serum with a focus in application to skeletal muscle cell lines (i.e., C2C12, L6, and LHCN-M2) and human primary skeletal muscle cells (HSMCs) as a means to investigate molecular signaling in models of atrophy and hypertrophy, alongside future directions.

The Impact of Slice Interval and Equation on the Accuracy of Magnetic Resonance Image Estimation of Quadriceps Muscle Volume in End Stage Liver Disease.

Introduction: End stage liver disease (ESLD) is associated with loss of muscle mass and function, known as sarcopenia, which can increase the risk of complications of ESLD, hospitalization and mortality. Therefore, the accurate assessment of muscle mass is essential to evaluate sarcopenia in ESLD. However, manual segmentation of muscle volume (MV) can be laborious on cross-sectional imaging, due to the number of slices that require analysis. This study aimed to investigate the impact of reducing the number of slices required for MV estimation. Further, we aimed to compare two equations utilized in estimating MV (cylindrical and truncated cone). Methods: Thirty eight ESLD patients (23 males; 54.8 ± 10.7 years) were recruited from the Queen Elizabeth University Hospital Birmingham. A 3T MRI scan was completed of the lower limbs. Quadriceps MV was estimated utilizing 1-, 2-, 3-, and 4 cm slice intervals with both cylindrical and truncated cone equations. Absolute and relative error (compared to 1 cm slice interval) was generated for 2-, 3-, and 4 cm slice intervals. L3 skeletal muscle index (SMI) was also calculated in 30 patients. Results: Relative error increased with slice interval using the cylindrical (0.45 vs. 1.06 vs. 1.72%) and truncated cone equation (0.27 vs. 0.58 vs. 0.74%) for 2, 3, and 4 cm, respectively. Significantly, the cylindrical equation produced approximately twice the error compared to truncated cone, with 3 cm (0.58 vs. 1.06%, P < 0.01) and 4 cm intervals (0.74 vs. 1.72%, P < 0.001). Finally, quadriceps MV was significantly correlated to L3 SMI (r 2 = 0.44, P < 0.0001). Conclusion: The use of the truncated equation with a 4 cm slice interval on MRI offers an efficient but accurate estimation of quadricep muscle volume in ESLD patients.

(-)-Epicatechin and its colonic metabolite hippuric acid protect against dexamethasone-induced atrophy in skeletal muscle cells.

Cocoa flavanols have been shown to improve muscle function and may offer a novel approach to protect against muscle atrophy. Hippuric acid (HA) is a colonic metabolite of (-)-epicatechin (EPI), the primary bioactive compound of cocoa, and may be responsible for the associations between cocoa supplementation and muscle metabolic alterations. Accordingly, we investigated the effects of EPI and HA upon skeletal muscle morphology and metabolism within an in vitro model of muscle atrophy. Under atrophy-like conditions (24h 100µM dexamethasone (DEX)), C2C12 myotube diameter was significantly greater following co-incubation with either 25µM HA (11.19±0.39µm) or 25µM EPI (11.01±0.21µm) compared to the vehicle control (VC; 7.61±0.16µm, both P < .001). In basal and leucine-stimulated states, there was a significant reduction in myotube protein synthesis (MPS) rates following DEX treatment in VC (P = .024). Interestingly, co-incubation with EPI or HA abrogated the DEX-induced reductions in MPS rates, whereas no significant differences versus control treated myotubes (CTL) were noted. Furthermore, co-incubation with EPI or HA partially attenuated the increase in proteolysis seen in DEX-treated cells, preserving LC3 α/ß II:I and caspase-3 protein expression in atrophy-like conditions. The protein content of PGC1α, ACC, and TFAM (regulators of mitochondrial function) were significantly lower in DEX-treated versus. CTL cells (all P < .050). However, co-incubation with EPI or HA was unable to prevent these DEX-induced alterations. For the first time we demonstrate that EPI and HA exert anti-atrophic effects on C2C12 myotubes, providing novel insight into the association between flavanol supplementation and favourable effects on muscle health.

No effect of five days of bed rest or short-term resistance exercise prehabilitation on markers of skeletal muscle mitochondrial content and dynamics in older adults.

Bed rest (BR) results in significant impairments in skeletal muscle metabolism. Mitochondrial metabolism is reportedly highly sensitive to disuse, with dysregulated fission-fusion events and impaired oxidative function previously reported. The effects of clinically relevant short-term BR (≤5 days) on mitochondrial protein expression are presently unclear, as are the effects of exercise prehabilitation as a potential counteractive intervention. The present study examined the effects of a 5-day period of BR and short-term resistance exercise prehabilitation (ST-REP) on mitochondrial-protein content. Ten older men (71 ± 4 years) underwent 5 days of BR, completing four sessions of high-volume unilateral resistance exercise prehabilitation over 7 days beforehand. Muscle biopsies were obtained from the vastus lateralis in the non-exercised control and exercised legs, both pre- and post-prehabilitation and pre- and post-BR, to determine changes in citrate synthase enzyme activity and the expression of key proteins in the mitochondrial electron transport chain and molecular regulators of fission-fusion dynamics, biosynthesis, and mitophagy. We observed no significant effect of either BR or ST-REP on citrate synthase protein content, enzyme activity, or ETC complex I-V protein content. Moreover, we observed no significant changes in markers of mitochondrial fission and fusion (p-DRP1S616 , p-DRP1S637 , p-DRP1S616/S637 ratio, p-MFFS146 , Mitofillin, OPA1, or MFN2 (p > 0.05 for all). Finally, we observed no differences in markers of biosynthesis (p-AMPKT172 , p-ACCS79 , PGC1a, TFAM) or mitophagy-related signaling (ULK-1, BNIP3/NIX, LC3B I/II) (p > 0.05 for all). In contrast to previous longer-term periods of musculoskeletal disuse (i.e., 7-14 days), a clinically relevant, 5-day period of BR resulted in no significant perturbation in muscle mitochondrial protein signaling in healthy older adults, with no effect of ST-REP in the week prior to BR. Accordingly, disuse-induced muscle atrophy may precede alterations in mitochondrial content.

The Effect of Ex Vivo Human Serum from Liver Disease Patients on Cellular Protein Synthesis and Growth.

Sarcopenia is a common complication affecting liver disease patients, yet the underlying mechanisms remain unclear. We aimed to elucidate the cellular mechanisms that drive sarcopenia progression using an in vitro model of liver disease. C2C12 myotubes were serum and amino acid starved for 1-h and subsequently conditioned with fasted ex vivo serum from four non-cirrhotic non-alcoholic fatty liver disease patients (NAFLD), four decompensated end-stage liver disease patients (ESLD) and four age-matched healthy controls (CON) for 4- or 24-h. After 4-h C2C12 myotubes were treated with an anabolic stimulus (5 mM leucine) for 30-min. Myotube diameter was reduced following treatment with serum from ESLD compared with CON (−45%) and NAFLD (−35%; p < 0.001 for both). A reduction in maximal mitochondrial respiration (24% and 29%, respectively), coupling efficiency (~12%) and mitophagy (~13%) was identified in myotubes conditioned with NAFLD and ESLD serum compared with CON (p < 0.05 for both). Myostatin (43%, p = 0.04) and MuRF-1 (41%, p = 0.03) protein content was elevated in myotubes treated with ESLD serum compared with CON. Here we highlight a novel, experimental platform to further probe changes in circulating markers associated with liver disease that may drive sarcopenia and develop targeted therapeutic interventions.

Acute resistance exercise training does not augment mitochondrial remodelling in master athletes or untrained older adults.

Background: Ageing is associated with alterations to skeletal muscle oxidative metabolism that may be influenced by physical activity status, although the mechanisms underlying these changes have not been unraveled. Similarly, the effect of resistance exercise training (RET) on skeletal muscle mitochondrial regulation is unclear. Methods: Seven endurance-trained masters athletes ([MA], 74 ± 3 years) and seven untrained older adults ([OC]. 69 ± 6 years) completed a single session of knee extension RET (6 x 12 repetitions, 75% 1-RM, 120-s intra-set recovery). Vastus lateralis muscle biopsies were collected pre-RET, 1 h post-RET, and 48h post-RET. Skeletal muscle biopsies were analyzed for citrate synthase (CS) enzyme activity, mitochondrial content, and markers of mitochondrial quality control via immunoblotting. Results: Pre-RET CS activity and protein content were ∼45% (p < .001) and ∼74% greater in MA compared with OC (p = .006). There was a significant reduction (∼18%) in CS activity 48 h post-RET (p < .05) in OC, but not MA. Pre-RET abundance of individual and combined mitochondrial electron transport chain (ETC) complexes I-V were significantly greater in MA compared with OC, as were markers of mitochondrial fission and fusion dynamics (p-DRP-1Ser616, p-MFFSer146, OPA-1 & FIS-1, p < .05 for all). Moreover, MA displayed greater expression of p-AMPKThr172, PGC1α, TFAM, and SIRT-3 (p < .05 for all). Notably, RET did not alter the expression of any marker of mitochondrial content, biogenesis, or quality control in both OC and MA. Conclusion: The present data suggest that long-term aerobic exercise training supports superior skeletal muscle mitochondrial density and protein content into later life, which may be regulated by greater mitochondrial quality control mechanisms and supported via superior fission-fusion dynamics. However, a single session of RET is unable to induce mitochondrial remodelling in the acute (1h post-RET) and delayed (48 h post-RET) recovery period in OC and MA.

Evaluation of the mechanisms of sarcopenia in chronic inflammatory disease: protocol for a prospective cohort study.

BACKGROUND: Several chronic inflammatory diseases co-exist with and accelerate sarcopenia (reduction in muscle strength, function and mass) and negatively impact on both morbidity and mortality. There is currently limited research on the extent of sarcopenia in such conditions, how to accurately assess it and whether there are generic or disease-specific mechanisms driving sarcopenia. Therefore, this study aims to identify potential mechanisms driving sarcopenia within chronic inflammatory disease via a multi-modal approach; in an attempt to help define potential interventions for future use. METHODS: This prospective cohort study will consist of a multi-modal assessment of sarcopenia and its underlying mechanisms. Recruitment will target three chronic inflammatory diseases: chronic liver disease (CLD) (n=50), with a subset of NAFLD (n=20), inflammatory bowel disease (IBD) (n=50) and rheumatoid arthritis (RA) (n=50) both before and after therapeutic intervention. In addition, 20 age and sex matched healthy individuals will be recruited for comparison. Participants will undergo 4 assessment visits at weeks 0, 2, 12 and 24. Visits will consist of the following assessments: blood tests, anthropometrics, functional assessment, quadriceps muscle imaging, actigraphy, quality of life questionnaires, food diary collection and muscle biopsy of the vastus lateralis (at weeks 2 and 24 only). In addition, stool and urine samples will be collected for future microbiome and metabolomics analysis. DISCUSSION: This is the first study to use a multi-modal assessment model to phenotype sarcopenia in these chronic inflammatory diseases. We hope to identify generic as well as disease-specific mechanisms driving sarcopenia. We appreciate that these cohorts do require separate standards of care treatments which limit comparison between groups. ETHICS AND DISSEMINATION: The study is approved by the Health Research Authority - West Midlands Solihull Research Ethics Service Committee Authority (REC reference: 18/WM/0167). Recruitment commenced in January 2019 and will continue until July 2021. The study was halted in March 2020 and again in January 2021 with the COVID-19 pandemic. The findings will be disseminated through peer-reviewed publications and conference presentations. All data will be stored on a secure server. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04734496.

Short-term step reduction reduces citrate synthase activity without altering skeletal muscle markers of oxidative metabolism or insulin-mediated signaling in young males.

Mitochondria are critical to skeletal muscle contractile function and metabolic health. Short-term periods of step reduction (SR) are associated with alterations in muscle protein turnover and mass. However, the effects of SR on mitochondrial metabolism/muscle oxidative metabolism and insulin-mediated signaling are unclear. We tested the hypothesis that the total and/or phosphorylated protein content of key skeletal muscle markers of mitochondrial/oxidative metabolism, and insulin-mediated signaling would be altered over 7 days of SR in young healthy males. Eleven, healthy, recreationally active males (means ± SE, age: 22 ± 1 yr, BMI: 23.4 ± 0.7 kg·m2) underwent a 7-day period of SR. Immediately before and following SR, fasted-state muscle biopsy samples were acquired and analyzed for the assessment of total and phosphorylated protein content of key markers of mitochondrial/oxidative metabolism and insulin-mediated signaling. Daily step count was significantly reduced during the SR intervention (13,054 ± 833 to 1,192 ± 99 steps·day-1, P < 0.001). Following SR, there was a significant decline in maximal citrate synthase activity (fold change: 0.94 ± 0.08, P < 0.05) and a significant increase in the protein content of p-glycogen synthase (P-GSS641; fold change: 1.47 ± 0.14, P < 0.05). No significant differences were observed in the total or phosphorylated protein content of other key markers of insulin-mediated signaling, oxidative metabolism, mitochondrial function, or mitochondrial dynamics (all P > 0.05). These results suggest that short-term SR reduces the maximal activity of citrate synthase, a marker of mitochondrial content, without altering the total or phosphorylated protein content of key markers of skeletal muscle mitochondrial metabolism and insulin signaling in young healthy males.NEW & NOTEWORTHY Short-term (7 day) step reduction reduces the activity of citrate synthase without altering the total or phosphorylated protein content of key markers of skeletal muscle mitochondrial metabolism and insulin signaling in young healthy males.

Efficacy of Dietary and Supplementation Interventions for Individuals with Type 2 Diabetes.

The prevalence of Type 2 diabetes (T2D) is increasing, which creates a large economic burden. Diet is a critical factor in the treatment and management of T2D; however, there are a large number of dietary approaches and a general lack of consensus regarding the efficacy of each. Therefore, the purpose of this narrative review is twofold: (1) to critically evaluate the effects of various dietary strategies on diabetes management and treatment, such as Mediterranean diet, plant-based diet, low-calorie and very low-calorie diets, intermittent fasting, low-carbohydrate and very low-carbohydrate diets, and low glycemic diets and (2) to examine several purported supplements, such as protein, branched-chain amino acids, creatine, and vitamin D to improve glucose control and body composition. This review can serve as a resource for those wanting to evaluate the evidence supporting the various dietary strategies and supplements that may help manage T2D.