Understanding the turnover of proteins in tissues gives information as to how external stimuli result in phenotypic change. Nowhere is such phenotypic change more conspicuous than skeletal muscle, which can be effectively remodelled by increased loading, ageing and unloading (disuse), all of which are subject to modification by nutrition and other environmental stimuli. The understanding of muscle proteome remodelling has undergone a renaissance recently with the reintroduction of deuterated water (D2O) and its ingestion to label amino acids and measure their incorporation into proteins. However, there is confusion around the use of the deuterated water methodology and the interpretation of the data it provides. Here, we provide a short review of some of the more salient features of the method and clarify some of the confusion around the method of deuterated water methods and its use in humans and how the interpretation of the data is in contrast to that of rodents.

Oxygen delivery and utilization to working muscle(s) are essential for sustained exercise performance. Higher contractile loads can occlude intramuscular blood vessels, limiting oxygen perfusion, while lighter loads minimize occlusion and allow perfusion. This study explored how external load impacted relative muscle endurance, work capacity, and muscle oxygenation in free-flow and cuff-occluded states to estimate the load at which a muscle occludes itself. Twenty-nine participants (10 untrained (UT), 9 endurance-trained (ET), 10 resistance-trained (RT); 14 females, 15 males) completed repetitions to task failure at 15%, 20%, 25%, 30%, 40%, and 80% of their unilateral knee-extension 1RM in free-flow and cuff-occluded states, with muscle oxygenation (SmO2) measured using near-infrared spectroscopy (NIRS). Compared to cuff-occlusion, greater work capacity and SmO2 were observed in the free-flow state at 15%-30% 1RM (p < 0.05), but no differences were seen at 40% and 80% 1RM (p ≥ 0.05). In the free-flow state above 40% 1RM, RT participants performed more work than UT and ET (p < 0.05), with no differences between UT and ET (p ≥ 0.05). At 25% and 30% 1RM, ET and RT participants performed more work than UT (p < 0.05), with no differences between ET and RT (p ≥ 0.05). At 15% and 20% 1RM, ET participants performed more work than UT and RT (p < 0.05). These results suggest a load range of > 30% but ≤ 40% 1RM may represent a phase transition in critical occluding tension of the quadriceps, with contractile induced occlusion occurring above this range, and perfusion occurring below.

High-intensity/sprint interval training (HIIT/SIT) improves aerobic and anaerobic performance, but it is unknown if HIIT/SIT increases strength, muscle mass/size, and muscle endurance (ME). We aimed to determine if HIIT/SIT increases strength, muscle mass/size, and ME. Databases (Ovid Medline, Sport Discus, EMBASE, and CINAHL) and the gray literature (Google Scholar) were searched for original research articles investigating the impact of HIIT/SIT on strength, muscle mass/size, and ME (23 March 2025). The risk of bias (ROB) was assessed via the Cochrane ROB 2 Tool. Meta-analyses were performed when three or more randomized controlled trials compared HIIT/SIT to a common comparator. Fifty-four studies were included (N = 1136). Twenty-five studies had a high ROB, while twenty-nine had some concerns. Standardized mean differences (SMD) (95% CI) of 0.16; (−0.09, 0.40), 0.33; (−0.21, 0.87) were observed for meta-analyses comparing the effect of HIIT/SIT to moderate intensity continuous training (MICT) and non-exercise controls (CON) on FFM, respectively. A meta-analysis comparing the effect of HIIT/SIT to resistance training (RT) on leg press strength yielded a SMD of −0.82; 95% CI: (−1.97, 0.33). HIIT/SIT may induce slightly greater gains than MICT and CON for FFM, while RT is likely superior to HIIT/SIT for improving leg press strength. However, the certainty of evidence is low, and 95% CIs intersect zero for all analyses.

Gene expression, protein content, and protein activity of regulators of collagen breakdown (MMPs and TIMPs) were elevated 72 but not 6 h after an acute bout of resistance exercise in healthy young and older human skeletal muscle, with similar baseline intramuscular collagen content. Young and older adults were healthy and matched for physical fitness, indicating that intramuscular collagen accumulation may be driven by factors other than aging per se.

Cardiorespiratory fitness (CRF) and muscular fitness are powerful confounders in age and sex-related comparisons. This paper provides a perspective on the benefits and limitations of matching participants by physical activity behaviour, objectively measured fitness and normative fitness percentiles. Data presented herein are a subset of a larger study, and highlight that matching by physical activity, does not necessarily match on other metrics like physical fitness, especially when age-related comparisons are being made. Our data showed that young and older adults matched by physical activity behaviours showed the expected higher CRF and muscular fitness in male and younger participants, but older adults had higher CRF percentiles. This suggests that matching by physical activity behaviour may select older adults with relatively higher CRF. Researchers must choose their matching method carefully to ensure the appropriate aspects of fitness have been matched between groups. For clarity, they should also report when certain aspects of fitness have not been accounted for and give an explanation as to why.

BACKGROUND:Assess the association between changes in injured leg knee extension and flexion strength (peak torque) and self-reported and performance-based measures of leg function after a variety of youth sport-related, time-loss knee injuries. HYPOTHESIS:There will be a relationship between changes in knee muscle strength and changes in measures of leg function in youth after a sport-related knee injury. STUDY DESIGN:Prospective cohort study. LEVEL OF EVIDENCE:Level 2. METHODS:This was a secondary analysis of the Alberta Youth Prevention of Early Osteoarthritis (PrEOA) Cohort study (Edmonton) that included youth (11-19 years old) who had experienced a medical attention, time-loss, sport-related knee injury in the previous 4 months. Injured leg knee extensor and flexor concentric peak torque (isokinetic; 90 deg/s), triple hop distance, modified Y-balance test (YBT), and Knee injury and Osteoarthritis Outcome Score Sport subscale (KOOSsport) were assessed at baseline (≤4 months postinjury) and 6 and 12 months later. Adjusted associations between 6- and 12-month change in strength and functional measures were assessed using multivariable regression (95% CI). RESULTS:Based on data from 106 participants (16.2 ± 1.8 years old), a 1 Nm increase in knee extensor strength (6-12 months) was associated with a 0.9 cm (95% CI, -0.5, 2.3) increase in hop distance. Similarly, every 1 Nm increase in knee flexor strength (6-12 months) was associated with a 0.3 cm (95% CI, -1.1, 1.7) increase in hop distance. Across other models, a 1 Nm increase in extensor or flexor strength was associated with a 0- to 0.3-point increase in KOOSsport score. CONCLUSION:There was minimal-to-no longitudinal relationship between changes in knee extensor or flexor strength and changes in triple hop or YBT performance, or self-reported function within the first year after a youth sport-related knee injury.

The purpose of this study was to compare quadriceps morphology between legs and individuals with a first-time anterior cruciate ligament (ACL) tear and uninjured controls. This was an exploratory cross-sectional study. We enrolled participants who were aged 19-35 years, and 6-60 months after a first-time ACL tear as well as uninjured controls. Participants attended two sessions separated by a minimum of 7 days. Bilateral knee extensor concentric and eccentric strength and rate of torque development (RTD) were assessed at the first session, and bilateral vastus lateralis muscle biopsies were obtained at the second. Muscle fiber-type specific cross-sectional area (fCSA), fiber-type proportions, and extracellular matrix area were calculated. Between-limb and between-group differences were estimated using mixed-effects regression. 41 of 47 (87%) participants completed the study (n = 21 ACL, n = 20 control). ACL group participants were a median (range) of 23 months from injury, and 78% had undergone an ACL reconstruction. Uninjured group participants had greater knee extensor concentric strength (-39.3 Nm; 95% CI: -54.2, -20.5), eccentric strength (-30.2 Nm; 95% CI: -53.4, -11.6), and RTD (-0.16 Nm/ms; 95% CI: -0.33, -0.04). No between-group or between-limb differences in muscle fiber-type specific fCSA, fiber-type proportions, or extracellular matrix area were observed. Despite deficits in knee extensor muscle performance, no difference in vastus lateralis fiber-type specific CSA, fiber-type proportion, or extracellular matrix area was detected between individuals 6-60 months after an ACL tear and uninjured controls.

A majority of human genes produce non-protein-coding RNA (ncRNA), and some have roles in development and disease. Neither ncRNA nor human skeletal muscle is ideally studied using short-read sequencing, so we used a customized RNA pipeline and network modelling to study cell-type specific ncRNA responses during muscle growth at scale. We completed five human resistance-training studies (n = 144 subjects), identifying 61% who successfully accrued muscle-mass. We produced 288 transcriptome-wide profiles and found 110 ncRNAs linked to muscle growth in vivo, while a transcriptome-driven network model demonstrated interactions via a number of discrete functional pathways and single-cell types. This analysis included established hypertrophy-related ncRNAs, including CYTOR-which was leukocyte-associated (false discovery rate [FDR] = 4.9 × 10-7). Novel hypertrophy-linked ncRNAs included PPP1CB-DT (myofibril assembly genes, FDR = 8.15 × 10-8), and EEF1A1P24 and TMSB4XP8 (vascular remodelling and angiogenesis genes, FDR = 2.77 × 10-5). We also discovered that hypertrophy lncRNA MYREM shows a specific myonuclear expression pattern in vivo. Our multi-layered analyses established that single-cell-associated ncRNA are identifiable from bulk muscle transcriptomic data and that hypertrophy-linked ncRNA genes mediate their association with muscle growth via multiple cell types and a set of interacting pathways.

High magnitude loading from performing resistance-based exercise has been found to improve tendon strength and reduce symptoms of Achilles tendinopathy (AT) but is difficult to quantify without specialist equipment. Here, we assess the validity and reliability of a novel AT rehabilitation tool (the "PhysViz" system) compared to a "gold-standard" dynamometer for assessing plantarflexion maximal voluntary isometric contractions (MVIC). 41 participants aged 18-60 completed the study. A within-subject test-retest study design was used to examine and compare the validity and reliability of the two systems during plantarflexion MVICs. Test - retest reliability of the two methods were determined by calculating intra-class correlation coefficients (ICCs) and 95% confidence intervals. Method agreement was assessed with Bland - Altman Limits of Agreement (LoA) analysis. The PhysViz demonstrated excellent test-retest reliability; ICC, SEM and MDC were numerically comparable to the dynamometer (ICC 0.93 vs. 0.92; SEM 2.01 vs. 2.95 kg and MDC 5.58 vs. 8.18 kg, respectively), indicating that the novel system is valid and reliable for measuring plantarflexor MVICs. Future studies should address its utility in monitoring AT rehabilitative loading remotely over time.

Background Metabolomic dysregulation following a meal in overweight individuals with the Metabolic Syndrome (MetS) involves multiple pathways of nutrient storage and oxidation. Objective The aim of the current study was to perform an acute cross-over intervention to examine the interactive actions of meal glycaemic load (GL) on the dynamic responses of the plasma metabolome in overweight females. Methods Postmenopausal women [63 ± 1.23y; Healthy ( n = 20) and MetS ( n = 20)] ingested two differing high-carbohydrate test meals (73 g carbohydrate; 51% energy) composed of either low glycemic index (LGI) or high (HGI) foods in a randomised sequence. Plasma metabolome was analysed using liquid chromatography–mass spectrometry (LC–MS). Results In the overweight women with MetS, there were suppressed postprandial responses for several amino acids (AAs), including phenylalanine, leucine, valine, and tryptophan, p < 0.05 ), irrespective of the meal type. Meal GL exerted a limited impact on the overall metabolomic response, although the postprandial levels of alanine were higher with the low GL meal and uric acid was greater following the high GL meal ( p < 0.05 ). Conclusions MetS participants exhibited reduced differences in the concentrations of a small set of AAs and a limited group of metabolites implicated in energy metabolism following the meals. However, the manipulation of meal GL had minimal impact on the postprandial metabolome. This study suggests that the GL of a meal is not a major determinant of postprandial response, with a greater impact exerted by the metabolic health of the individual. Trial registration Australia New Zealand Clinical Trials Registry: ACTRN12615001108505 (21/10/2015)

Cold water immersion (CWI) following intense exercise is a common athletic recovery practice. However, CWI impacts muscle adaptations to exercise training, with attenuated muscle hypertrophy and increased angiogenesis. Tissue temperature modulates the abundance of specific miRNA species and thus CWI may affect muscle adaptations via modulating miRNA expression following a bout of exercise. The current study focused on the regulatory mechanisms involved in cleavage and nuclear export of mature miRNA, including DROSHA, EXPORTIN-5, and DICER. Muscle biopsies were obtained from the vastus lateralis of young males (n = 9) at rest and at 2, 4, and 48 h of recovery from an acute bout of resistance exercise, followed by either 10 min of active recovery (ACT) at ambient temperature or CWI at 10°C. The abundance of key miRNA species in the regulation of intracellular anabolic signaling (miR-1 and miR-133a) and angiogenesis (miR-15a and miR-126) were measured, along with several gene targets implicated in satellite cell dynamics (NCAM and PAX7) and angiogenesis (VEGF and SPRED-1). When compared to ACT, CWI suppressed mRNA expression of DROSHA (24 h p = 0.025 and 48 h p = 0.017), EXPORTIN-5 (24 h p = 0.008), and DICER (24 h p = 0.0034). Of the analyzed miRNA species, miR-133a (24 h p < 0.001 and 48 h p = 0.007) and miR-126 (24 h p < 0.001 and 48 h p < 0.001) remained elevated at 24 h post-exercise in the CWI trial only. Potential gene targets of these miRNA, however, did not differ between trials. CWI may therefore impact miRNA abundance in skeletal muscle, although the precise physiological relevance needs further investigation.

Muscle fatigue is defined as a reduction in the capability of muscle to exert force or power. Although surface electromyography (sEMG) signals during exercise have been used to assess muscle fatigue, analyzing the sEMG signal during dynamic contractions is difficult because of the many signal distorting factors such as electrode movements, and variations in muscle tissue conductivity. Besides the non-deterministic and non-stationary nature of sEMG in dynamic contractions, no fatigue indicator is available to predict the ability of a muscle to apply force based on the sEMG signal properties.In this study, we designed and manufactured a novel wearable sensor system with both sEMG electrodes and motion tracking sensors to monitor the dynamic muscle movements of human subjects. We detected the state of muscle fatigue using a new wavelet analysis method to predict the maximum isometric force the subject can apply during dynamic con-traction.Our method of signal processing consists of four main steps. 1-Segmenting sEMG signals using motion tracking signals. 2-Determine the most suitable mother wavelet for discrete wavelet transformation (DWT) based on cross-correlation between wavelets and signals. 3-Deoinsing the sEMG using the DWT method. 4-Calculation of normalized energy in differ-ent decomposition levels to predict maximal voluntary isometric contraction force as an indicator of muscle fatigue.The monitoring system was tested on healthy adults doing biceps curl exercises, and the results of the wavelet decomposition method were compared to well-known muscle fatigue indices in the literature.(c) 2023 Nalecz Institute of Biocybernetics and Biomedical Engineering of the Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

Ectopic lipid accumulation, including intra-pancreatic fat deposition (IPFD), exacerbates type 2 diabetes risk in susceptible individuals. Dysregulated circulating microRNAs (miRNAs) have been identified as correlating with clinical measures of pancreatitis, pancreatic cancer and type 1 diabetes. The aim of the current study was therefore to examine the association between circulating abundances of candidate miRNAs, IPFD and liver fat deposition as quantified using magnetic resonance imaging (MRI) and spectroscopy (MRS). Asian Chinese (n = 34; BMI = 26.7 ± 4.2 kg/m2) and European Caucasian (n = 34; BMI = 28.0 ± 4.5 kg/m2) females from the TOFI_Asia cohort underwent MRI and MRS analysis of pancreas (MR-%IPFD) and liver fat (MR-%liver fat), respectively, to quantify ectopic lipid deposition. Plasma miRNA abundances of a subset of circulatory miRNAs associated with IPFD and liver fat deposition were quantified by qRT-PCR. miR-21-3p and miR-320a-5p correlated with MR-%IPFD, plasma insulin and HOMA2-IR, but not MR-%liver fat. MR-%IPFD remained associated with decreasing miR-21-3p abundance following multivariate regression analysis. miR-21-3p and miR-320a were demonstrated to be negatively correlated with MR-%IPFD, independent of ethnicity. For miR-21-3p, this relationship persists with the inclusion of MR-%liver fat in the model, suggesting the potential for a wider application as a specific circulatory correlate of IPFD.

Background: Many individuals develop excess skin (ES) following massive weight loss (MWL). Patient-reported outcomes demonstrate that abdominal ES negatively impacts perceived physical function which is improved by abdominal body contouring surgery (ABCS). However, the effect of ABCS on objective measures of physical function is unknown. Objectives: The aim of this study was to examine the impact of ABCS on objective measures of physical function in individuals who have undergone MWL. Methods: Patients who have undergone MWL with abdominal ES (grade, >= 2) underwent the following physical function assessments: 9-item modified physical performance test (mPPT), chair stand, star excursion balance test (SEBT), timed up and go (TUG), modified agility T test, and 6-minute walk test (6-MWT). Perception of physical exertion and BODY-Q questionnaire scales were also collected. Nonsurgical controls (n = 21) and those who had undergone ABCS (n = 6) after the first visit performed a second physical function assessment 8 to 12 weeks later to allow for postoperative healing. Results: No ceiling or floor effect was detected for any physical function measure. The intraclass correlation coefficient was 0.78 (95% CI, 0.44, 0.91) for the mPPT and >0.80 for all other measures. The effect sizes were 0.74 (75% CI, 0.19, 1.28) for the mPPT, 0.54 (75% CI, 0.00,1.08) for the SEBT, -0.63 (75% CI, -117, -0.09) for the modified agility T test, and 0.79 (75% CI, 0.24, 0.13) for the 6-MWT. Conclusions: The mPPT and tests involving dynamic balance, agility, and walking were reliable and showed medium to large effect sizes, suggesting that these tests may be sensitive to change following ABCS.

The effect of resistance training with higher-and lower-loads on muscle mass and strength has been extensively studied, while changes in muscle endurance have received less attention. This trial aimed to assess the effect of training load on absolute muscle endurance (AME) and relative muscle endurance (RME). Sixteen untrained women (22.7 +/- 3.3 yr: mean +/- SD) had one arm and leg randomly assigned to train with higher loads (HL; 80-90% 1RM), and the contralateral limbs trained with lower loads (LL; 30-50% 1RM) thrice weekly to volitional fatigue for 10 weeks. Heavy and light load AME and RME, strength, and muscle mass were assessed pre-and post-training. Strength increased more in the HL compared to LL leg (P < 0.01), but similar increases in strength were observed between upper body conditions (P = 0.46). Lower body heavy and light load AME improved in both conditions, but HL training induced a larger improvement in heavy load AME (HL: 9.3 +/- 4.3 vs. LL: 7.5 +/- 7.1 repetitions, time x limb P < 0.01) and LL training induced a larger improvement in light load AME (LL: 24.7 +/- 22.2 vs. HL: 15.2 +/- 16.7 repetitions, time x limb P = 0.04). In the upper body, HL and LL training induced similar increases in both heavy (time x limb P = 0.99), and light load (time x limb P = 0.16) AME. Dual-energy X-ray absorptiometry showed no change in leg fat-and-bone-free mass (FBFM) for either condition, and an increase in only LL arm FBFM. AME improved in a manner specific to the training loads used. ClinicalTrials.gov (NCT04547972).

Unaccustomed exercise causes muscle damage resulting in loss of muscle function, which may be attributable to exercise-induced increases in skeletal muscle reactive oxygen species. This study examined the effect of mitochondria-targeted antioxidant supplementation on recovery of muscle function following exercise. Thirty-two untrained men received MitoQ (20 mg/day) or a placebo for 14 days before performing 300 maximal eccentric contractions of the knee extensor muscles of 1 leg. Muscle function was assessed using isokinetic dynamometry before, immediately after, and 24, 48, 72, and 168 hours after exercise. Muscle soreness was assessed using a visual analogue scale 24, 48, 72, and 168 hours after exercise. Blood samples were collected before, immediately after, and 2, 24, 48, 72, and 168 hours after exercise and urine samples were collected before and during the 48 hours after exercise. The reduction in maximal voluntary isometric contraction force and peak concentric torque following exercise was unaffected by MitoQ while recovery of peak eccentric torque was delayed in the MitoQ group. Exercise-induced increases in urine F2-isoprostanes were unaffected by MitoQ. MitoQ augmented exercise-induced increases in plasma creatine kinase levels, while plasma IL-6 was similar between groups. Muscle soreness was not affected by MitoQ. These results indicate that MitoQ does not attenuate post-exercise muscle soreness and may delay recovery of muscle function following eccentric exercise. Trial registration number: ACTRN12620001089921. Novelty: Post-exercise recovery of maximal voluntary isometric contraction force and peak concentric torque were unaffected by MitoQ. MitoQ delayed post-exercise recovery of peak eccentric torque. Post-exercise muscle soreness was unaffected by MitoQ.

The role of mitochondrial ROS in signalling muscle adaptations to exercise training has not been explored in detail. We investigated the effect of supplementation with the mitochondria-targeted antioxidant MitoQ on a) the skeletal muscle mitochondrial and antioxidant gene transcriptional response to acute high-intensity exercise and b) skeletal muscle mitochondrial content and function following exercise training. In a randomised, double-blind, placebo-controlled, parallel design study, 23 untrained men (age: 44 ± 7 years, VO2peak: 39.6 ± 7.9 ml/kg/min) were randomised to receive either MitoQ (20 mg/d) or a placebo for 10 days before completing a bout of high-intensity interval exercise (cycle ergometer, 10 × 60 s at VO2peak workload with 75 s rest). Blood samples and vastus lateralis muscle biopsies were collected before exercise and immediately and 3 h after exercise. Participants then completed high-intensity interval training (HIIT; 3 sessions per week for 3 weeks) and another blood sample and muscle biopsy were collected. There was no effect of acute exercise or MitoQ on systemic (plasma protein carbonyls and reduced glutathione) or skeletal muscle (mtDNA damage and 4-HNE) oxidative stress biomarkers. Acute exercise-induced increases in skeletal muscle peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α) mRNA expression were augmented in the MitoQ group. Despite this, training-induced increases in skeletal muscle mitochondrial content were similar between groups. HIIT-induced increases in VO2peak and 20 km time trial performance were also similar between groups while training-induced increases in peak power achieved during the VO2peak test were augmented in the MitoQ group. These data suggest that training-induced increases in peak power are enhanced following MitoQ supplementation, which may be related to the augmentation of skeletal muscle PGC1α expression following acute exercise. However, these effects do not appear to be related to an effect of MitoQ supplementation on exercise-induced oxidative stress or training-induced mitochondrial biogenesis in skeletal muscle.

Mitochondrial dynamics are regulated by the differing molecular pathways variously governing biogenesis, fission, fusion, and mitophagy. Adaptations in mitochondrial morphology are central in driving the improvements in mitochondrial bioenergetics following exercise training. However, there is a limited understanding of mitochondrial dynamics in response to inactivity. Skeletal muscle biopsies were obtained from middle-aged males (n = 24, 49.4 ± 3.2 years) who underwent sequential 14-day interventions of unilateral leg immobilisation, ambulatory recovery, and resistance training. We quantified vastus lateralis gene and protein expression of key proteins involved in mitochondrial biogenesis, fusion, fission, and turnover in at baseline and following each intervention. PGC1α mRNA decreased 40

Exercise increases skeletal muscle reactive oxygen species (ROS) production, which may contribute to the onset of muscular fatigue and impair athletic performance. Mitochondria-targeted antioxidants such as MitoQ, which contains a ubiquinone moiety and is targeted to mitochondria through the addition of a lipophilic triphenylphosphonium cation, are becoming popular amongst active individuals as they are designed to accumulate within mitochondria and may provide targeted protection against exercise-induced oxidative stress. However, the effect of MitoQ supplementation on cycling performance is currently unknown. Here, we investigate whether MitoQ supplementation can improve cycling performance measured as time to complete an 8 km time trial. In a randomized, double-blind, placebo-controlled crossover study, 19 middle-aged (age: 44 ± 4 years) recreationally trained (VO2peak: 58.5 ± 6.2 ml·kg− 1·min− 1, distance cycled per week during 6 months prior to study enrollment: 158.3 ± 58.4 km) male cyclists completed 45 min cycling at 70% VO2peak followed by an 8 km time trial after 28 days of supplementation with MitoQ (20 mg·day− 1) and a placebo. Free F2-isoprostanes were measured in plasma samples collected at rest, after 45 min cycling at 70% VO2peak and after completion of the time trial. Respiratory gases and measures of rating of perceived exertion (RPE) were also collected. Mean completion time for the time trial was 1.3% faster with MitoQ (12.91 ± 0.94 min) compared to placebo (13.09 ± 0.95 min, p = 0.04, 95% CI [0.05, 2.64], d = 0.2). There was no difference in RPE during the time trial between conditions (p = 0.82) despite there being a 4.4% increase in average power output during the time trial following MitoQ supplementation compared to placebo (placebo; 270 ± 51 W, MitoQ; 280 ± 53 W, p = 0.04, 95% CI [0.49, 8.22], d = 0.2). Plasma F2-isoprostanes were lower on completion of the time trial following MitoQ supplementation (35.89 ± 13.6 pg·ml− 1) compared to placebo (44.7 ± 16.9 pg·ml− 1 p = 0.03). These data suggest that MitoQ supplementation may be an effective nutritional strategy to attenuate exercise-induced increases in oxidative damage to lipids and improve cycling performance.

Objectives: Dietary strategies to promote successful aging are divergent. Higher-protein diets are recommended to preserve skeletal muscle mass and physical function. Conversely, increased B-vitamin intake, supporting one-carbon (1C) metabolism, reduces the risk of cognitive decline and cardiovascular disease. On the hypothesis that higher protein intake through animal-based sources will benefit 1C regulation by the supply of B vitamins (folate, riboflavin, and vitamins B-6 and B-12) and methyl donors (choline) despite higher methionine intake, this study explored the effect of a higher-protein diet on 1C metabolite status in older men compared to current protein recommendations. Methods: Older men (age, 74 +/- 3 y) were randomized to receive a diet for 10 wk containing either the recommended dietary allowance (RDA) of protein (0.8 g/kg body weight/d, n = 14), or double that amount (2RDA, n = 15), with differences in protein accounted for by modifying carbohydrate intake. Intervention diets were matched to each individual's energy requirements based on the Harris-Benedict equation and adjusted fortnightly as required depending on physical activity and satiety. Fasting plasma 1C metabolite concentrations were quantified by liquid chromatography coupled with mass spectrometry at baseline and after 10 wk of intervention. Results: Plasma homocysteine concentrations were reduced from baseline to follow-up with both diets. Changes in metabolite ratios reflective of betaine-dependent homocysteine remethylation were specific to the RDA diet, with an increase in the betaine-to-choline ratio and a decrease in the dimethylglycine-to-betaMe ratio. Comparatively, increasing folate intake was positively associated with a change in choline concentration and inversely with the betaine-to-choline ratio for the 2RDA group. Conclusions: Adding to the known benefits of higher protein intake in older people, this study supports a reduction of homocysteine with increased consumption of animal-based protein, although the health effects of differential response of choline metabolites to a higher-protein diet remain uncertain. (C) 2021 Elsevier Inc. All rights reserved.