Hibernation is an extreme adaptation that enables a diverse array of mammalian species to survive long-term nutrient deprivation. In many seasonal hibernators, winter hibernation is characterized by prolonged periods of immobility and starvation, conditions that induce muscular atrophy in nonhibernating animals. In humans, factors that contribute to muscle atrophy include muscle disuse under conditions of bedrest, casting, paralysis, microgravity, as well as aging. In laboratory mice and rats, muscle disuse can be induced by hindlimb unloading or casting-experimental paradigms that have revealed the molecular basis of muscle atrophy. Remarkably, hibernating mammals experience reduced atrophy and maintain muscle ultrastructure and function despite months of immobility and starvation, serving as excellent models for investigating protective mechanisms for muscular atrophy resistance. In this review, we explore skeletal muscle homeostasis at multiple levels of biological organization, from function, neural innervation, gross anatomy, cellular differentiation, ultrastructure, to biochemical pathways regulating regeneration, growth, and degeneration. At each level, we compare known mechanisms in hibernators, laboratory rodents, and humans. Finally, we highlight gaps in knowledge and propose future areas of investigation for elucidating mechanisms of muscle atrophy resistance in hibernation.

The study investigated the influence of mental fatigue on older people's enjoyment during a series of physical exercises. Using a randomized cross-over design, participants (n = 35) completed a 6-minute walking test - 6MWT, a Timed Up and Go-TUG test and three sets of knee extension exercise (first set: KE1, second set: KE2, third set: KE3) under two experimental conditions (control or mental fatigue). The Nonparametric Analysis of Longitudinal Data in Factorial Experiments was used to compare the number of repetitions performed during three sets of resistance exercise between conditions. The same analysis method was applied to compare the perception of effort and enjoyment across five moments (Post-6MWT, Post-TUG, Post-KE1, Post-KE2, Post-KE3) and two conditions and the Visual Analogue Scales (VAS) across four moments (baseline, Pre-6MWT, Pre-TUG, Pre-KE) and two conditions. Mental fatigue did not affect the physical function, perception of effort and enjoyment of exercise in older people. Participants, however, reported higher enjoyment for walking and dynamic balance compared to strength exercise. Mental fatigue had no effect on the physical function, perception of effort and enjoyment of exercise of older people. Participants presented a higher enjoyment for walking and dynamic balance compared to strength exercise. Given the importance of resistance exercises for health, clinicians should prioritize resources to education programs emphasizing the benefits of resistance exercise in both short- and long-term health. Including social interaction opportunities in physical exercise programs and prescribing activities appropriate to participants' ability levels could enhance engagement and adherence.

Background/Objectives: In this study, we aimed to examine the effect of creatine monohydrate (CrM) supplementation on recovery from eccentric exercise-induced muscle damage (EIMD) in diverse populations, including different sexes and age groups. EIMD decreases maximal voluntary contraction (MVC), restricts the range of motion (ROM), and increases muscle stiffness and delayed-onset muscle soreness, all of which negatively impact athletic performance. Therefore, developing effective recovery strategies is essential. Methods: A double-blind, randomized, placebo-controlled trial was conducted with 40 healthy male and female participants. After 33 days of supplementation with either CrM or placebo (crystalline cellulose), the participants performed eccentric exercises. Recovery indices, including MVC, muscle stiffness, subjective muscle extensive soreness, fatigue, and upper arm circumference, were measured at baseline, immediately after exercise, 48 h post-exercise, and 96 h post-exercise. Results: The creatine supplementation group (CRE) demonstrated a significantly quicker recovery of MVC than the placebo group (PLA). Furthermore, reductions in shear modulus and muscle fatigue were observed in the CRE group. Notably, females in the CRE group exhibited a significant suppression of post-exercise edema, suggesting a sex-specific response. Conclusions: These findings indicate that CrM supplementation may enhance recovery from EIMD, contributing to the maintenance of muscle function and the reduction of discomfort after exercise. CrM has the potential to serve as a practical nutritional strategy to promote recovery, not only for athletes, but also for a broader population.

Aging is the primary risk factor for the development of many chronic diseases, including dementias, cardiovascular disease, and diabetes. There is significant interest in identifying novel "geroprotective" agents, including by repurposing existing drugs, but such treatments may affect organ systems differently. One current example is the nucleoside reverse transcriptase inhibitor 3TC, which has been increasingly studied as a potential gerotherapeutic. Recent data suggest that 3TC may reduce inflammation and improve cognitive function in older mice; however, the effects of 3TC on other tissues in aged animals are less well characterized. Here, we use transcriptomics (RNA-seq) and targeted metabolomics to investigate the influence of 3TC supplementation on skeletal muscle in older mice. We show that 3TC 1) does not overtly affect muscle mass or functional/health markers, 2) largely reverses age-related changes in gene expression and metabolite signatures, and 3) is potentially beneficial for mitochondrial function in old animals via increases in antioxidant enzymes and decreases in mitochondrial reactive oxygen species. Collectively, our results suggest that, in addition to its protective effects in other tissues, 3TC supplementation does not have adverse effects in aged muscle and may even protect muscle/mitochondrial health in this context.NEW & NOTEWORTHY Recent studies suggest that the nucleoside reverse transcriptase inhibitor 3TC may improve brain health and cognitive function in old mice, but its effects on other aging tissues have not been comprehensively studied. This is the first study to use a multiomics approach to investigate the effects of 3TC treatment on skeletal muscle of old mice. The results suggest that 3TC reverses age-related transcriptomic and metabolite signatures and is potentially beneficial for mitochondrial function in aged muscle.

Body composition and functional capacity are both related to physical activity, but the interplay is complex, as different body tissue types contribute differently on physical activity and functional capacity. To clarify the role of body composition and functional capacity as determinants of physical activity in aging, we investigated the associations of different body tissue types, muscle strength, and walking capacity with physical activity in middle-aged and older adults.

This cross-sectional study involved 1158 women aged 47-55 years, and community-dwelling 289 women and 196 men aged 75, 80, or 85 years. Their physical activity was assessed with accelerometers, muscle mass and muscle-free mass with bioelectrical impedance analysis, walking performance with a six-minute walking test, and muscle strength with maximal isometric knee extension test. The associations of muscle mass, muscle-free mass, walking performance, and muscle strength with physical activity were studied separately for middle-aged women, older women, and older men using linear regression and structural equation models.

Total body mass and absolute muscle-free mass were inversely associated with the level of physical activity in all study groups. Furthermore, walking performance, muscle strength, and muscle mass relative to body weight, but not absolute muscle mass, were directly associated with the level of physical activity. The associations between the measures of body composition and physical activity were fully explained by the differences in functional capacity, as defined by both walking performance and muscle strength, in structural equation models. Functional capacity was strongly associated with higher levels of physical activity regardless of body composition, especially among older people: β = 0.70, SE = 0.10 for older women, β = 0.92, SE = 0.27 for older men, and β = 0.41, SE = 0.10 for middle-aged women.

Reduced functional capacity may be a key factor limiting physical activity, with its impact becoming more pronounced as functional capacity declines with age. Based on these findings, maintaining and improving functional capacity is essential for promoting an active lifestyle in older adults.

The relationship between testosterone levels and muscle mass and strength remains contentious. This study aimed to explore the relationship among total serum testosterone levels, muscle mass, and strength in young to middle-aged adults.

The analysis included 4,495 participants (age 39.2 ± 0.2 years, mean ± SE) from the National Health and Nutrition Examination Survey conducted between 2011 and 2014. Weighted regression models were used to assess the association of testosterone levels with muscle mass and strength.

For male participants, log2-transformed testosterone levels were positively associated with appendicular lean mass adjusted for body mass index (β: 0.05, 95% confidence interval [CI]: 0.03-0.07, P < 0.001) and negatively associated with low muscle mass (odds ratio: 0.40, 95% CI: 0.24-0.67, P = 0.006). However, no significant association was found between testosterone levels and grip strength (β: 1.16, 95% CI: 0.26 to 2.58, P = 0.086) or low muscle strength (odds ratio: 0.51, 95% CI: 0.25-1.04, P = 0.059). For female participants, no significant association was observed between testosterone levels and muscle mass (β: 0.01, 95% CI: 0.02 to -0.01, P = 0.294) or muscle strength (β: 0.14, 95% CI: 0.45 to 0.73, P = 0.508). Restricted cubic spline analysis revealed a linear relationship between total testosterone levels and appendicular lean mass adjusted for body mass index in male participants (nonlinear: P = 0.367).

Our study indicates that testosterone levels are positively associated with muscle mass but not with muscle strength in young to middle-aged males.

Resistive squat exercise is a well-established technique to enhance the strength of muscles and bones of the back extensors in humans. Rehabilitation programs aimed at strengthening the muscles and bone of the back require the knowledge of the patient's 1 repetition maximum (RM) of squat exercise. Finding the 1RM value of squat exercise could lead to injury or seem nonfeasible because of the higher weights involved, especially in older adults.

To investigate the predictive relationship between the maximum voluntary isometric squat strength and the 1RM concentric and eccentric squat strength in young and older individuals.

In our cross-sectional study, individuals from two age populations, 21-35 years (young) and 55-75 years (older) were recruited and participated in two visits within a two-week period. Our main outcome measures were: Maximum voluntary isometric squat strength (IsoMax) and 1RM of concentric (ConMax) and eccentric (EccMax) back squat strength were calculated for young and older adults. All the strength measures were normalized for body weight.

IsoMax was a significant predictor of the ConMax (p = 0.003; Normalized ConMax = 0.708 + 1.376(Normalized IsoMax); 95%CI: 0.583-2.169) and EccMax (p = 0.003, Normalized EccMax = 0.844 + 1.433(Normalized IsoMax); 95%CI = 0.582-2.284) in older adults only. There was a trend toward significance for the relationship between IsoMax and ConMax (p = 0.058) in young adults.

Our novel findings show that safe techniques for muscle strength assessment, such as maximum voluntary isometric squat strength, can be utilized in older populations to predict their 1RM of concentric and eccentric squat strength. Our novel equations provide the information necessary for designing effective rehabilitation regimes for strengthening the muscles and bone of the back in older adults.

Background and Clinical Significance: Sarcopenia, characterized by muscle loss and fat infiltration, poses a significant health burden for aging populations. Quantitative Color 2D and 3D radiodensitometry provides a powerful tool to monitor muscle quality and quantity through CT imaging. This study assessed the impact of a ten-year-long home-bed gym exercise intervention on muscle quality in an elderly subject using CT-derived radiodensitometric analysis. The study involved two comparative analyses: Study A, which compared knee-to-ankle CT scans of the subject between 2013 and 2023; and Study B, which compared the subject's 2023 thigh CT scan with a cohort of 2500 elderly Icelandic individuals from the AGES-Reykjavik study.

A 70-year-old male began a home-based Full-Body In-Bed Gym exercise program in 2013. Quantitative muscle volume and radiodensity measurements were performed using CT at baseline and after ten years.

Study A shows significant improvements in muscle volume observed in the knee-to-ankle region, while a slower decline in radiodensity was noted, indicating substantial preservation of muscle quality despite the expected decay of ten-year aging. For instance, muscle volume increased by 15% in the left Soleus muscle and by 6% in the right Soleus muscle, while the average radiodensity decreased by 12-17 HU. The subject's thigh muscle quality at 80-years-old is above the AGES-Reykjavik's cohort average, with reduced fat infiltration.

Long-term home Full-Body In-Bed Gym, a low-impact exercise, can mitigate aging sarcopenia, as evidenced by improved tissue radiodensity and muscle mass substantial preservation. This suggests potential applications in personalized healthcare strategies to enhance muscle preservation among aging populations.

Age-related changes occurring in the kidney can lead to a reduction in Glomerular Filtration Rate (GFR); especially in older adults with multimorbidity and/or frailty, an accurate evaluation of kidney function is critical. For the estimation of GFR in patients over 70 years, CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) is often used. However, validated equations exist for old-age populations like BIS1 (Berlin Initiative Study 1) and FAS (Full Age Spectrum). Here we aimed to compare the performance of CKD-EPI, MDRD (Modification of Diet in Renal Disease), BIS1, and FAS in assessing eGFR in a population of patients over 70, to evaluate which equations show the most accurate performance in our setting.

A total of 499 older adults were consecutively recruited in the Orthogeriatric ward and Oncogeriatrics clinic of IRCCS Polyclinic San Martino in Genoa Italy. eGFR was calculated using CKD-EPI, MDRD, BIS1, and FAS, calculating mean, median, standard deviation, and interquartile range. Bland-Altman graphs were used to evaluate how each equation performs with respect to the others and the concordance of the attribution of the KDIGO CKD stage was performed with Cohen's K constant and chi-squared test.

Patients' mean age was 82.6 years (± 7.44), and the mean creatinine value was 0.97 (± 0.71) mg/dl. The mean value of eGFR was 70 mL/min with CKD-EPI (± 20.6) and MDRD (± 25.7), 57 mL/min with BIS1 (± 16.7) and FAS (± 19.0), respectively. BIS1 and FAS estimated lower eGFR values than CKD-EPI and MDRD. As age increases, a steady decrease in filtrate value is observed with BIS1 and FAS. MDRD and CDK-EPI do not show the same trend. The performance of the equations at a fixed eGFR value of 30 mL/min is more linear for BIS1 and FAS compared with CKD-EPI and MDRD. Upon evaluation with chi-square, the attribution of KDIGO stage was statistically different among the various equations.

An appropriate assessment of renal function is of key clinical relevance to prevent adverse outcomes and risk of drug accumulation in older adults. Our study originally showed that in persons aged more than 70 years old BIS1 is the most accurate formula in calculating eGFR values when only serum creatinine is available.

Human studies examining the cellular mechanisms behind sarcopenia, or age-related loss of skeletal muscle mass and function, have produced inconsistent results. A systematic review and meta-analysis were performed to determine the aging effects on protein expression, size, and distribution of fibers with various myosin heavy chain (MyHC) isoforms. Study eligibility included MyHC comparisons between young (18-49 yr) and older (≥60 yr) adults, with 27 studies identified. Relative protein expression was higher with age for the slow-contracting MyHC I fibers, with correspondingly lower fast-contracting MyHC II and IIA values. Fiber sizes were similar with age for MyHC I, but smaller for MyHC II and IIA. Fiber distributions were similar with age. When separated by sex, the few studies that examined females showed atrophy of MyHC II and IIA fibers with age, but no change in MyHC protein expression. Additional analyses by measurement technique, physical activity, and muscle biopsies provided important insights. In summary, age-related atrophy in fast-contracting fibers lead to more of the slow-contracting, lower force-producing isoform in older male muscles, which helps explain their age-related loss in whole muscle force, velocity, and power. Exercise or pharmacological interventions that shift MyHC expression toward faster isoforms and/or increase fast-contracting fiber size should decrease the prevalence of sarcopenia. Our findings also indicate that future studies need to include or focus solely on females, measure MyHC IIA and IIX isoforms separately, examine fiber type distribution, sample additional muscles to the vastus lateralis (VL), and incorporate an objective measurement of physical activity.

Emerging evidence indicates that intravenous ketamine is effective in managing treatment-resistant unipolar and bipolar depression. Clinical studies highlight its favorable efficacy, safety, and tolerability profile within a dosage range of 0.5-1.0 mg/kg based on actual body weight. However, data on alternative dosage calculation methods, particularly in relation to body mass index (BMI) and therapeutic outcomes, remain limited.

This retrospective analysis of an open-label study aims to evaluate dose calculation strategies and their impact on treatment response among inpatients with treatment-resistant major depressive disorder (MDD) (n = 28). The study employed the Boer and Devine formulas to determine lean body mass (LBM) and ideal body weight (IBW), and the Mosteller formula to estimate body surface area (BSA). The calculated doses were then compared with the actual doses administered or converted to a dosage per square meter for both responders and non-responders.

Regardless of treatment response, defined as a reduction of 50% in the Montgomery-Åsberg Depression Rating Scale, the use of alternative ketamine dosing formulas resulted in underdosing compared to the standardized dose of 0.5 mg/kg. Only two participants received higher doses (102.7% and 113.0%) when the Devine formula was applied.

This study suggests that ketamine dosing formulas, alternative to the standardized 0.5 mg/kg based on body weight, may lead to underdosing and potentially impact outcome interpretation. To enhance dosing accuracy, future studies should consider incorporating body impedance analysis and waist-to-hip ratio measurements, as this study did not account for body composition.

During skeletal muscle adaptation to physiological or pathophysiological signals, contractile apparatus and mitochondrial function are coordinated to alter muscle fiber type. Although recent studies have identified various factors involved in modifying contractile proteins and mitochondrial function, the molecular mechanisms coordinating contractile and metabolic functions during muscle fiber transition are not fully understood. Using a gene-deficient mouse approach, our previous studies uncovered that vestigial-like family member 2 (Vgll2), a skeletal muscle-specific transcription cofactor activated by exercise, is essential for fast-to-slow adaptation of skeletal muscle. The current study provides evidence that Vgll2 plays a role in increasing muscle mitochondrial mass and oxidative capacity. Transgenic Vgll2 overexpression in mice altered muscle fiber composition toward the slow type and enhanced exercise endurance, which contradicted the outcomes observed with Vgll2 deficiency. Vgll2 expression was positively correlated with the expression of genes related to mitochondrial function in skeletal muscle, mitochondrial DNA content, and protein abundance of oxidative phosphorylation complexes. Additionally, Vgll2 overexpression significantly increased the maximal respiration of isolated muscle fibers and enhanced the suppressive effects of endurance training on weight gain. Notably, no additional alteration in expression of myosin heavy chain genes was observed after exercise, suggesting that Vgll2 plays a direct role in regulating mitochondrial function, independent of its effect on contractile components. The observed increase in exercise endurance and metabolic efficiency may be attributed to the acute upregulation of genes promoting fatty acid utilization as a direct consequence of Vgll2 activation facilitated by endurance exercise. Thus, the current study establishes that Vgll2 is an integrative regulator of mitochondrial function and contractility in skeletal muscle.

In this study, we aimed to determine the effects of 2-week neuromuscular electrical stimulation (NMES) on quadriceps muscle atrophy and lower extremity motor score in individuals with subacute incomplete cervical spinal cord injury (SCI).

This stratified randomized controlled trial, conducted in the advanced critical care center of a university hospital, comprised 49 individuals with American Spinal Injury Association (ASIA) impairment scale grade C and D incomplete cervical SCI. The participants were stratified based on the ASIA impairment scale grade and randomly assigned to the control (n = 25) or NMES (n = 24) group. The control group participants received only conventional rehabilitation; the NMES group participants received conventional rehabilitation plus NMES in the quadriceps muscles of both lower limbs. The primary endpoints were quadriceps muscle thickness and L3 ASIA lower extremity motor score (L3 motor score), measured at the study's initiation and after 2 weeks.

The quadriceps muscle thickness changes on the stronger and weaker sides were -14.2% ± 11.3% and -15.1% ± 13.8%, respectively, in the NMES group and -25.7% ± 16.8% and -26.0% ± 13.3%, respectively, in the control group, indicating significantly lesser reduction on both sides in the NMES group (p <0.05). The L3 motor scores on the stronger and weaker sides were 0.8 ± 1.2 and 1.3 ± 1.4 (NMES group) and 0.4 ± 0.8 and 0.4 ± 0.8 (control group), respectively, indicating significant improvement only on the weaker side (p <0.05).

For subacute incomplete cervical SCI, 2 weeks of NMES reduces quadriceps muscle atrophy and improves the L3 motor score values on the weaker side compared with standard treatment.

Skeletal muscle plays a crucial role in generating force to facilitate movement. Skeletal muscle is a heterogenous tissue composed of diverse fibers with distinct contractile and metabolic profiles. The intricate classification of skeletal muscle fibers exists on a continuum ranging from type I (slow-twitch, oxidative) to type II (fast-twitch, glycolytic). The heterogenous distribution and characteristics of fibers within and between skeletal muscles profoundly influences cellular signaling; however, this has not been broadly discussed as it relates to macroautophagy/autophagy. The growing interest in skeletal muscle autophagy research underscores the necessity of comprehending the interplay between autophagic responses among skeletal muscles and fibers with different contractile properties, metabolic profiles, and other related signaling processes. We recommend approaching the interpretation of autophagy findings with careful consideration for two key reasons: 1) the distinct behaviors and responses of different skeletal muscles or fibers to various perturbations, and 2) the potential impact of alterations in skeletal muscle fiber type or metabolic profile on observed autophagic outcomes. This review provides an overview of the autophagic profile and response in skeletal muscles/fibers of different types and metabolic profiles. Further, this review discusses autophagic findings in various conditions and diseases that may differentially affect skeletal muscle. Finally, we provide key points of consideration to better enable researchers to fine-tune the design and interpretation of skeletal muscle autophagy experiments.Abbreviation: AKT1: AKT serine/threonine kinase 1; AMPK: AMP-activated protein kinase; ATG: autophagy related; ATG4: autophagy related 4 cysteine peptidase; ATG5: autophagy related 5; ATG7: autophagy related 7; ATG12: autophagy related 12; BECN1: beclin 1; BNIP3: BCL2 interacting protein 3; CKD: chronic kidney disease; COPD: chronic obstructive pulmonary disease; CS: citrate synthase; DIA: diaphragm; EDL: extensor digitorum longus; FOXO3/FOXO3A: forkhead box O3; GAS; gastrocnemius; GP: gastrocnemius-plantaris complex; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAPK: mitogen-activated protein kinase; MYH: myosin heavy chain; PINK1: PTEN induced kinase 1; PLANT: plantaris; PRKN: parkin RBR E3 ubiquitin protein ligase; QUAD: quadriceps; RA: rectus abdominis; RG: red gastrocnemius; RQ: red quadriceps; SOL: soleus; SQSTM1: sequestosome 1; TA: tibialis anterior; WG: white gastrocnemius; WQ: white quadriceps; WVL: white vastus lateralis; VL: vastus lateralis; ULK1: unc-51 like autophagy activating kinase 1.

Although it is clear that the bioenergetic basis of skeletal muscle fatigue (transient decrease in peak torque or power in response to contraction) involves intramyocellular acidosis (decreased pH) and accumulation of inorganic phosphate (Pi) in response to the increased energy demand of contractions, the effects of old age on the build-up of these metabolites has not been evaluated systematically. The purpose of this study was to compare pH and [Pi] in young (18-45 yr) and older (55+ yr) human skeletal muscle in vivo at the end of standardized contraction protocols. Full study details were prospectively registered on PROSPERO (CRD42022348972). PubMed, Web of Science, and SPORTDiscus databases were systematically searched and returned 12 articles that fit the inclusion criteria for the meta-analysis. Participant characteristics, contraction mode (isometric, dynamic), and final pH and [Pi] were extracted. A random-effects model was used to calculate the mean difference (MD) and 95% confidence interval (CI) for pH and [Pi] across age groups. A subgroup analysis for contraction mode was also performed. Young muscle acidified more than older muscle (MD = -0.12 pH; 95%CI = -0.18,-0.06; p<0.01). There was no overall difference by age in final [Pi] (MD = 2.14 mM; 95%CI = -0.29,4.57; p = 0.08), although sensitivity analysis revealed that removing one study resulted in greater [Pi] in young than older muscle (MD = 3.24 mM; 95%CI = 1.72,4.76; p<0.01). Contraction mode moderated these effects (p = 0.02) such that young muscle acidified (MD = -0.19 pH; 95%CI = -0.27,-0.11; p<0.01) and accumulated Pi (MD = 4.69 mM; 95%CI = 2.79,6.59; p<0.01) more than older muscle during isometric, but not dynamic, contractions. The smaller energetic perturbation in older muscle indicated by these analyses is consistent with its relatively greater use of oxidative energy production. During dynamic contractions, elimination of this greater reliance on oxidative energy production and consequently lower metabolite accumulations in older muscle may be important for understanding task-specific, age-related differences in fatigue.

Sarcopenia is a progressive disorder characterized by age-related loss of skeletal muscle mass and function. Although significant progress has been made over the years to identify the molecular determinants of sarcopenia, the precise mechanisms underlying the age-related loss of contractile function remains unclear. Advances in "omics" technologies, including mass spectrometry-based proteomic and metabolomic analyses, offer great opportunities to better understand sarcopenia. Herein, we performed mass spectrometry-based analyses of the vastus lateralis from young, middle-aged, and older rhesus monkeys to identify molecular signatures of sarcopenia. In our proteomic analysis, we identified proteins that change with age, including those involved in adenosine triphosphate and adenosine monophosphate metabolism as well as fatty acid beta oxidation. In our untargeted metabolomic analysis, we identified metabolites that changed with age largely related to energy metabolism including fatty acid beta oxidation. Pathway analysis of age-responsive proteins and metabolites revealed changes in muscle structure and contraction as well as lipid, carbohydrate, and purine metabolism. Together, this study discovers new metabolic signatures and offers new insights into the molecular mechanisms underlying sarcopenia for the evaluation and monitoring of a therapeutic treatment of sarcopenia.

The objective of this study is to understand the role of vitamin B12 supplementation in improving skeletal muscle function among the elderly.

A literature review in the Medline database was conducted to understand the association between vitamin B12 and muscle function in Section A. In Section B, 28 healthy elderly participants aged ≥60 years were recruited in a cross-sectional design for estimation of plasma vitamin B12 status and assessment of upper limb muscle strength Maximal voluntary contraction (MVC) and muscle quality (expressed as MVC/total muscle mass). Participants were grouped based on vitamin B12 status into vitamin B12-depleted (<148 pmol/L) and replete (≥148 pmol/L) groups. In a quasi-experimental study design, the vitamin B12-depleted group (n = 14) received daily oral vitamin B12 supplementation of 100 μg for 3 months. All the study measures were repeated post-supplementation.

Vitamin B12 deficiency was identified to contribute adversely to muscle strength, quality, and physical performance among older people in the extensive literature review. The pilot intervention study showed significant improvement in MVC and muscle quality (p < 0.050) post-vitamin B12 supplementation, comparable to the vitamin B12-replete group.

Vitamin B12 may have a crucial role in the maintenance of muscle function. 3-month oral vitamin B12 supplementation among subclinical vitamin B12 deficient elderly improved muscle strength and quality and reached levels similar to the vitamin B12 replete group.

The aim of this study was to provide a scoping and comprehensive review for the clinical outcomes from the cross-link of Type 2 diabetes mellitus (T2DM), COVID-19, and sarcopenia.

By using PRISMA guidelines and searching through different databases that could provide findings of evidence on the association of T2DM, COVID-19, and sarcopenia.

Thirty-three studies reported a relationship between sarcopenia with T2DM, twenty-one studies reported the prognosis COVID-19 in patients with T2DM, ten studies reported the prognosis of COVID-19 in patients with sarcopenia, five studies discussed the outcomes of sarcopenia in patients with COVID-19, and one study reported sarcopenia outcomes in the presence of T2DM and COVID-19.

There is an obvious multidimensional relationship between T2DM, COVID-19 and sarcopenia which can cause prejudicial effects, poor prognosis, prolonged hospitalisation, lowered quality of life and a higher mortality rate during the current COVID-19 pandemic.

Quantitative imaging in life sciences has evolved into a powerful approach combining advanced microscopy acquisition and automated analysis of image data. The focus of the present study is on the imaging-based evaluation of the posterior cricoarytenoid muscle (PCA) influenced by long-term functional electrical stimulation (FES), which may assist the inspiration of patients with bilateral vocal fold paresis. To this end, muscle cross-sections of the PCA of sheep were examined by quantitative image analysis. Previous investigations of the muscle fibers and the collagen amount have not revealed signs of atrophy and fibrosis due to FES by a laryngeal pacemaker. It was therefore hypothesized that regardless of the stimulation parameters the fat in the muscle cross-sections would not be significantly altered. We here extending our previous investigations using quantitative imaging of intramuscular fat in cross-sections. In order to perform this analysis both reliably and faster than a qualitative evaluation and time-consuming manual annotation, the selection of the automated method was of crucial importance. To this end, our recently established deep neural network IMFSegNet, which provides more accurate results compared to standard machine learning approaches, was applied to more than 300 H&E stained muscle cross-sections from 22 sheep. It was found that there were no significant differences in the amount of intramuscular fat between the PCA with and without long-term FES, nor were any significant differences found between the low and high duty cycle stimulated groups. This study on a human-like animal model not only confirms the hypothesis that FES with the selected parameters has no negative impact on the PCA, but also demonstrates that objective and automated deep learning-based quantitative imaging is a powerful tool for such a challenging analysis.

Findings from a recent 70-day bedrest investigation suggested intermittent exercise testing in the control group may have served as a partial countermeasure for skeletal muscle size, function, and fiber-type shifts. The purpose of the current study was to investigate the metabolic and skeletal muscle molecular responses to the testing protocols. Eight males (29 ± 2 yr) completed muscle power (6 × 4 s; peak muscle power: 1,369 ± 86 W) and V̇o2max (13 ± 1 min; 3.2 ± 0.2 L/min) tests on specially designed supine cycle ergometers during two separate trials. Blood catecholamines and lactate were measured pre-, immediately post-, and 4-h postexercise. Muscle homogenate and muscle fiber-type-specific [myosin heavy chain (MHC) I and MHC IIa] mRNA levels of exercise markers (myostatin, IκBα, myogenin, MuRF-1, ABRA, RRAD, Fn14, PDK4) and MHC I, IIa, and IIx were measured from vastus lateralis muscle biopsies obtained pre- and 4-h postexercise. The muscle power test altered (P ≤ 0.05) norepinephrine (+124%), epinephrine (+145%), lactate (+300%), and muscle homogenate mRNA (IκBα, myogenin, MuRF-1, RRAD, Fn14). The V̇o2max test altered (P ≤ 0.05) norepinephrine (+1,394%), epinephrine (+1,412%), lactate (+736%), and muscle homogenate mRNA (myostatin, IκBα, myogenin, MuRF-1, ABRA, RRAD, Fn14, PDK4). In general, both tests influenced MHC IIa muscle fibers more than MHC I with respect to the number of genes that responded and the magnitude of response. Both tests also influenced MHC mRNA expression in a muscle fiber-type-specific manner. These findings provide unique insights into the adaptive response of skeletal muscle to small doses of exercise and could help shape exercise dosing for astronauts and Earth-based individuals.NEW & NOTEWORTHY Declines in skeletal muscle health are a concern for astronauts on long-duration spaceflights. The current findings add to the growing body of exercise countermeasures data, suggesting that small doses of specific exercise can be beneficial for certain aspects of skeletal muscle health. This information can be used in conjunction with other components of existing exercise programs for astronauts and might translate to other areas focused on skeletal muscle health (e.g., sports medicine, rehabilitation, aging).

Based on the largely untested premise that it is a restorative hormone that may reverse the detrimental impacts of aging, prescription of testosterone (T) has increased in recent decades despite no new clinical indications. It is apparent that middle-aged and older men with low-normal serum T levels are considering T supplementation as an anti-aging strategy. At the same time, there is evidence that physical activity (PA) is at historical lows in the Western world. In this review, we compare the impacts of T treatment aimed at achieving physiological T concentrations in middle-aged and older men, alongside the impacts of ecologically relevant forms of exercise training. The independent, and possible combined, effects of T and exercise therapy on physiological outcomes such as aerobic fitness, body composition and muscular strength are addressed.

Our findings suggest that both T treatment and exercise improve lean body mass in healthy older men. If improvement in lean body mass is the primary aim, then T treatment could be considered, and the combination of T and exercise may be more beneficial than either in isolation. In terms of muscle strength in older age, an exercise program is likely to be more beneficial than T treatment (where the dose is aimed at achieving physiological concentrations), and the addition of such T treatment does not provide further benefit beyond that of exercise alone. For aerobic fitness, T at doses aimed at achieving physiological concentrations has relatively modest impacts, particularly in comparison to exercise training, and there is limited evidence as to additive effects. Whilst higher doses of T, particularly by intramuscular injection, may have larger impacts on lean body mass and strength, this must be balanced against potential risks.

Knowing the impacts of T treatment and exercise on variables such as body composition, strength and aerobic fitness extends our understanding of the relative benefits of physiological and pharmacological interventions in aging men. Our review suggests that T has impacts on strength, body composition and aerobic fitness outcomes that are dependent upon dose, route of administration, and formulation. T treatment aimed at achieving physiological T concentrations in middle-aged and older men can improve lean body mass, whilst exercise training enhances lean body mass, aerobic fitness and strength. Men who are physically able to exercise safely should be encouraged to do so, not only in terms of building lean body mass, strength and aerobic fitness, but for the myriad health benefits that exercise training confers.

Experimental techniques in single human skeletal muscle cells require manual dissection. Unlike other mammalian species, human skeletal muscle is characterized by a heterogeneous mixture of myosin heavy chain (MHC) isoforms, typically used to define "fiber type," which profoundly influences cellular function. Therefore, it is beneficial to predict MHC isoform at the time of dissection, facilitating a more balanced fiber-type distribution from a potentially imbalanced sample. Although researchers performing single fiber dissection report predicting fiber-type based on mechanical properties of fibers upon dissection, a rigorous examination of this approach has not been performed. Therefore, we measured normalized fiber length (expressed as a % of the length of the bundle from which the fiber was dissected) in single fibers immediately following dissection. Six hundred sixty-eight individual fibers were dissected from muscle tissue samples from healthy, young adults to assess whether this characteristic could differentiate fibers containing MHC I ("slow" fiber type) or not ("fast" fiber type). Using receiver operator characteristic (ROC) curves, we found that differences in normalized fiber length (114 ± 13%, MHC I; 124 ± 17%, MHC IIA, P < 0.01) could be used to predict fiber type with excellent reliability (area under the curve = 0.72). We extended these analyses to include older adults (2 females, 1 male) to demonstrate the durability of this approach in fibers with likely different morphology and mechanical characteristics. We report that MHC isoform expression in human skeletal muscle fibers can be predicted at the time of dissection, regardless of origin.NEW & NOTEWORTHY A priori estimation of myosin heavy chain (MHC) isoform in individual muscle fibers may bias the relative abundance of fiber types in subsequent assessment. Until now, no standardized assessment approach has been proposed to characterize fibers at the time of dissection. We demonstrate an approach based on normalized fiber length that may dramatically bias a sample toward slow twitch (MHC I) or fast twitch (not MHC I) fiber populations.

Sarcopenia is a significant health concern primarily affecting old adult individuals, characterized by age-related muscle loss, and decreased strength, power, and endurance. It has profound negative effects on overall health and quality of life, including reduced independence, mobility, and daily activity performance, osteoporosis, increased fall and fracture risks, metabolic issues, and chronic diseases like diabetes and cardiovascular conditions. Preventive strategies typically involve a combination of proper nutrition and regular physical activity. Among strength training exercises, high-intensity interval training (HIIT) stands out as the most effective approach for improving muscle function in older adults with sarcopenia. The current review identifies and summarizes the studies that have examined the effects of HIIT on muscle strength in older adults as an element of the prevention and treatment of sarcopenia. A systematic search using several computerized databases, namely, MEDLINE/PubMed, Scopus, SPORTDiscus, and Web of Science, was performed on 12 January 2023, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 224 studies were initially retrieved. A total of five studies met the selection criteria. HIIT training shows improvements in body composition and functional and cardiorespiratory capacity, has benefits on muscle strength, increases muscle quality and architecture, and is associated with muscle hypertrophy in healthy older adults. Nonetheless, given the shortcomings affecting primary research in terms of the limited number of studies and the high risk of bias, further research is warranted.

Skeletal muscle plays critical roles in providing a protein source and contributing to meat production. It is well known that microRNAs (miRNAs) exert important effects on various biological processes in muscle, including cell fate determination, muscle fiber morphology, and structure development. However, the role of miRNA in skeletal muscle development remains incompletely understood. In this study, we observed a critical miRNA, miR-24-3p, which exhibited higher expression levels in Tongcheng (obese-type) pigs compared to Landrace (lean-type) pigs. Furthermore, we found that miR-24-3p was highly expressed in the dorsal muscle of pigs and the quadriceps muscle of mice. Functionally, miR-24-3p was found to inhibit proliferation and promote differentiation in muscle cells. Additionally, miR-24-3p was shown to facilitate the conversion of slow muscle fibers to fast muscle fibers and influence the expression of GLUT4, a glucose transporter. Moreover, in a mouse model of skeletal muscle injury, we demonstrated that overexpression of miR-24-3p promoted rapid myogenesis and contributed to skeletal muscle regeneration. Furthermore, miR-24-3p was found to regulate the expression of target genes, including Nek4, Pim1, Nlk, Pskh1, and Mapk14. Collectively, our findings provide evidence that miR-24-3p plays a regulatory role in myogenesis and fiber type conversion. These findings contribute to our understanding of human muscle health and have implications for improving meat production traits in livestock.

Mechanical perturbation triggers activation of resident myogenic stem cells to enter the cell cycle through a cascade of events including hepatocyte growth factor (HGF) release from its extracellular tethering and the subsequent presentation to signaling-receptor c-met. Here, we show that with aging, extracellular HGF undergoes tyrosine-residue (Y) nitration and loses c-met binding, thereby disturbing muscle homeostasis. Biochemical studies demonstrated that nitration/dysfunction is specific to HGF among other major growth factors and is characterized by its locations at Y198 and Y250 in c-met-binding domains. Direct-immunofluorescence microscopy of lower hind limb muscles from three age groups of rat, provided direct in vivo evidence for age-related increases in nitration of ECM-bound HGF, preferentially stained for anti-nitrated Y198 and Y250-HGF mAbs (raised in-house) in fast IIa and IIx myofibers. Overall, findings highlight inhibitory impacts of HGF nitration on myogenic stem cell dynamics, pioneering a cogent discussion for better understanding age-related muscle atrophy and impaired regeneration with fibrosis (including sarcopenia and frailty).

Ultra-endurance events have gained global participation, whereas the critical factors of competition results remain to be well elucidated. This study used a nutritional approach to evaluate the association of competition results with carbohydrate intake and blood glucose control during a 100-mile ultramarathon. This observational study was conducted in the 2021 LAKE BIWA 100, which covered 100 miles (169 km) and 10,500 m elevation. The course was divided into 9 segments by aid station. According to the competition results, 22 participants (18 men and 4 women) were divided into higher finishers (n = 7), lower finishers (n = 9), and non-finishers (n = 6). The participants self-recorded their overall dietary intake throughout the race. Glucose levels were monitored every 15 min by a flash glucose monitoring system. Running speed in each segment was standardized to the average of the top five finishers for each gender. Among finishers, the carbohydrate intakes were significantly higher in the higher finishers than in the lower finishers during overall segments, especially in the first half of the race (p < 0.05). There was a significant positive correlation between running speed and carbohydrate intake in the lower finishers (rho = 0.700, p = 0.036). Two-way ANOVA analysis revealed that lowering glucose levels in each segment were more frequently observed in the lower finishers compared to the higher finishers (p = 0.012). Compared to the higher finishers, the lower finishers exhibited significantly greater fluctuations (⊿highest-lowest) in glucose levels (p < 0.001). The fluctuations in glucose levels were significantly and negatively correlated with the running speed of the finishers (rho =  - 0.612, p = 0.012). Faster runners consume high amounts of carbohydrates and maintain glucose levels during the 100-mile ultramarathon on the trail, especially at the beginning. Lowering and fluctuating glucose levels during the race are associated with lower running speed in endurance athletes.

To investigate differences in diffusion tensor imaging (DTI) parameters and proton density fat fraction (PDFF) in the spinal muscles of younger and older adult males.

Twelve younger (19-30 years) and 12 older (61-81years) healthy, physically active male participants underwent T1W, T2W, Dixon and DTI of the lumbar spine. The eigenvalues (λ1, λ2, and λ3), fractional anisotropy (FA), and mean diffusivity (MD) from the DTI together with the PDFF were determined in the multifidus, medial and lateral erector spinae (ESmed, ESlat), and quadratus lumborum (QL) muscles. A two-way ANOVA was used to investigate differences with age and muscle and t-tests for differences in individual muscles with age.

The ANOVA gave significant differences with age for all DTI parameters and the PDFF (P < .01) and with muscle (P < .01) for all DTI parameters except for λ1 and for the PDFF. The mean of the eigenvalues and MD were lower and the FA higher in the older age group with differences reaching statistical significance for all DTI measures for ESlat and QL (P < .01) but only in ESmed for λ3 and MD (P < .05).

Differences in DTI parameters of muscle with age result from changes in both in the intra- and extra-cellular space and cannot be uniquely explained in terms of fibre length and diameter.

Previous studies looking at age have used small groups with uneven age spacing. Our study uses two well defined and separated age groups.

Aging is typically associated with decreased muscle strength and rate of force development (RFD), partly explained by motor unit remodeling due to denervation, and subsequent loss of fast-twitch type II myofibers. Exercise is commonly advocated to counteract this detrimental loss. However, it is unclear how life-long strength versus endurance training may differentially affect markers of denervation and reinnervation of skeletal myofibers and, in turn, affect the proportion and morphology of fast-twitch type II musculature. Thus, we compared fiber type distribution, fiber type grouping, and the prevalence of atrophic myofibers (≤1,494 µm2) in strength-trained (OS) versus endurance-trained (OE) master athletes and compared the results to recreationally active older adults (all >70 yr, OC) and young habitually active references (<30 yr, YC). Immunofluorescent stainings were performed on biopsy samples from vastus lateralis, along with leg press maximal strength and RFD measurements. OS demonstrated similar type II fiber distribution (OS: 52.0 ± 16.4%; YC: 51.1 ± 14.4%), fiber type grouping, maximal strength (OS: 170.0 ± 18.9 kg, YC: 151.0 ± 24.4 kg), and RFD (OS: 3,993 ± 894 N·s-1, YC: 3,470 ± 1,394 N·s-1) as young, and absence of atrophic myofibers (OS: 0.2 ± 0.7%; YC: 0.1 ± 0.4%). In contrast, OE and OC exhibited more atrophic fibers (OE: 1.2 ± 1.0%; OC: 1.1 ± 1.4%), more grouped fibers, and smaller proportion of type II fibers (OE: 39.3 ± 11.9%; OC: 35.0 ± 12.4%) than OS and YC (all P < 0.05). In conclusion, strength-trained master athletes were characterized by similar muscle morphology as young, which was not the case for recreationally active or endurance-trained old. These results indicate that strength training may preserve type II fibers with advancing age in older men, likely as a result of chronic use of high contractile force generation.NEW & NOTEWORTHY Aging is associated with loss of fast-twitch type II myofibers, motor unit remodeling, and grouping of myofibers. This study reveals, for the first time, that strength training preserves neural innervation of type II fibers, resulting in similar myofiber type distribution and grouping in life-long strength-trained master athletes as young moderately active adults. In contrast, life-long endurance-trained master athletes and recreationally active old adults demonstrated higher proportion of type I fibers accompanied by more marked grouping of type I myofibers, and more atrophic fibers compared with strength-trained master athletes and young individuals. Thus, strength training should be utilized as a training modality for preservation of fast-twitch musculature, maximal muscle strength, and rapid force capacity (RFD) with advancing age.

Aging leads to a decline in muscle mass and force-generating capacity. Ultrasound shear wave elastography (SWE) is a non-invasive method to capture age-related muscular adaptation. This study assessed biceps brachii muscle (BB) mechanics, hypothesizing that shear elastic modulus reflects (i) passive muscle force increase imposed by length change, (ii) activation-dependent mechanical changes, and (iii) differences between older and younger individuals. Fourteen healthy volunteers aged 60-80 participated. Shear elastic modulus, surface electromyography, and elbow torque were measured at five elbow positions in passive and active states. Data collected from young adults aged 20-40 were compared. The BB passive shear elastic modulus increased from flexion to extension, with the older group exhibiting up to 52.58% higher values. Maximum elbow flexion torque decreased in extended positions, with the older group 23.67% weaker. Significant effects of elbow angle, activity level, and age on total and active shear elastic modulus were found during submaximal contractions. The older group had 20.25% lower active shear elastic modulus at 25% maximum voluntary contraction. SWE effectively quantified passive and activation-dependent BB mechanics, detecting age-related alterations at rest and during low-level activities. These findings suggest shear elastic modulus as a promising biomarker for identifying altered muscle mechanics in aging.

Introduction: A regular physical training is known to contribute to preserve muscle mass and strength, maintaining structure and function of neural and vascular compartments and preventing muscle insulin resistance and inflammation. However, physical activity is progressively reduced during aging causing mobility limitations and poor quality of life. Although physical exercise for rehabilitation purposes (e.g., after fractures or cardiovascular events) or simply aiming to counteract the development of sarcopenia is frequently advised by physicians, nevertheless few data are available on the targets and the global effects on the muscle organ of adapted exercise especially if started at old age. Methods: To contribute answering this question for medical translational purposes, the proteomic profile of the gastrocnemius muscle was analyzed in 24-month-old mice undergoing adapted physical training on a treadmill for 12 weeks or kept under a sedentary lifestyle condition. Proteomic data were implemented by morphological and morphometrical ultrastructural evaluations. Results and Discussion: Data demonstrate that muscles can respond to adapted physical training started at old age, positively modulating their morphology and the proteomic profile fostering protective and saving mechanisms either involving the extracellular compartment as well as muscle cell components and pathways (i.e., mitochondrial processes, cytoplasmic translation pathways, chaperone-dependent protein refolding, regulation of skeletal muscle contraction). Therefore, this study provides important insights on the targets of adapted physical training, which can be regarded as suitable benchmarks for future in vivo studies further exploring the effects of this type of physical activity by functional/metabolic approaches.

Aging is associated with neuromuscular system changes that may have implications for the recruitment and firing behaviors of motor units (MUs). In previous studies, we observed that young adults recruit subpopulations of triceps surae MUs during tasks that involved leaning in five directions: common units that were active during different leaning directions and unique units that were active in only one leaning direction. Furthermore, the MU subpopulation firing behaviors [average firing rate (AFR), coefficient of variation (CoVISI), and intermittent firing] modulated with leaning direction. The purpose of this study was to examine whether older adults exhibited this regional recruitment of MUs and firing behaviors. Seventeen older adults (aged 74.8 ± 5.3 yr) stood on a force platform and maintained their center of pressure leaning in five directions. High-density surface electromyography recordings from the triceps surae were decomposed into single MU action potentials. A MU tracking analysis identified groups of MUs as being common or unique across the leaning directions. Although leaning in different directions did not affect the AFR and CoVISI of common units (P > 0.05), the unique units responded to the leaning directions by increasing AFR and CoVISI, albeit modestly (F = 18.51, P < 0.001). The unique units increased their intermittency with forward leaning (F = 9.22, P = 0.003). The mediolateral barycenter positions of MU activity in both subpopulations were found in similar locations for all leaning directions (P > 0.05). These neuromuscular changes may contribute to the reduced balance performance seen in older adults.NEW & NOTEWORTHY In this study, we observed differences in motor unit recruitment and firing behaviors of distinct subpopulations of motor units in the older adult triceps surae muscle from those observed in the young adult. Our results suggest that the older adult central nervous system may partially lose the ability to regionally recruit and differentially control motor units. This finding may be an underlying cause of balance difficulties in older adults during directionally challenging leaning tasks.

While the butterfly stroke has received considerable attention in sports science, the origin of the fastest master butterfly swimmers remains unknown. The present study investigated which geographical locations produce the top-performing master butterfly swimmers within their age groups and gender. A total of 26,512 master butterfly swimmers (11,288 women and 15,224 men) competed in 50 m, 100 m and 200 m races in World Masters Championships held between 1986 and 2019. From each swimmer, the year of competition, first name, last name, age group and distance were recorded. Descriptive data were presented using mean, standard deviation, maximum and minimum values, and/or confidence intervals. The top 10 race times for master butterfly swimming and gender were identified for descriptive purposes. Nationalities were then grouped into six categories: the top five nationalities with the most appearances in the top 10 fastest times in butterfly swimming by distance each year and one group consisting of all other nationalities. In the event of a tie, the nationality with the most participants overall was selected. Generalized linear models (GLMs) with a gamma probability distribution and log link function were used to assess the effect of age groups and gender on swimming time. In summary, Germany had the fastest women butterfly master swimmers across all distances, while the USA had the fastest men butterfly master swimmers for all distances. Men covered all distances faster than women and younger swimmers were quicker than older swimmers. The results of this study can be utilized to determine the countries that produce the most successful master butterfly swimmers, providing a foundation for further research to explore the factors that lead to their success.

Facioscapulohumeral muscular dystrophy (FSHD) is caused by the aberrant expression of the double homeobox 4 (DUX4) gene. The FLExDUX4 mouse model carries an inverted human DUX4 transgene which has leaky DUX4 transgene expression at a very low level. No overt muscle pathology was reported before 16 weeks. The purpose of this study is to track and characterize the FLExDUX4 phenotypes for a longer period, up to one year old. In addition, transcriptomic changes in the muscles of 2-month-old mice were investigated using RNA-seq. The results showed that male FLExDUX4 mice developed more severe phenotypes and at a younger age in comparison to the female mice. These include lower body and muscle weight, and muscle weakness measured by grip strength measurements. Muscle pathological changes were observed at older ages, including fibrosis, decreased size of type IIa and IIx myofibers, and the development of aggregates containing TDP-43 in type IIb myofibers. Muscle transcriptomic data identified early molecular changes in biological pathways regulating circadian rhythm and adipogenesis. The study suggests a slow progressive change in molecular and muscle phenotypes in response to the low level of DUX4 expression in the FLExDUX4 mice.

With extended life expectancy, the quality of life of elders is a priority. Loss of mobility, increased morbidity and risks of falls have dramatic individual and societal impacts. Here we consider the age-related modifications of gait, from a biomechanical and neurophysiological perspective. Among the many factors of frailty involved (e.g., metabolic, hormonal, immunological), loss of muscle strength and neurodegenerative changes inducing slower muscle contraction may play a key role. We highlight that the impact of the multifactorial age-related changes in the neuromuscular systems results in common features of gait in the immature gait of infants and older adults. Besides, we also consider the reversibility of age-related neuromuscular deterioration by, on the one hand, exercise training, and the other hand, novel techniques such as direct spinal stimulation (tsDCS).

Although physical performance tests of the lower extremities are used to assess sarcopenia and frailty, little is known about the mechanisms by which the parameters of ground reaction force (GRF) measured during sit-to-stand motion affect the frailty status in older adults. We aimed to examine the association between GRF parameters during sit-to-stand motion and the incidence of frailty in older adults.

This longitudinal study evaluated 319 outpatients aged ≥ 65 years with cardiometabolic diseases. The GRF parameters were measured using a motor function analyzer, in which the power, speed, and balance scores were calculated. Frailty was diagnosed using the modified version of the Cardiovascular Health Study (mCHS) and the Kihon Checklist (KCL). The independent associations between scores and frailty indices were assessed using multivariate binomial logistic regression analyses. Cox regression analysis was used to examine whether power and speed scores were associated with the incidence of frailty after adjusting for covariates.

Logistic regression analyses adjusted for covariates showed that the power and speed scores were associated with frailty according to the mCHS criteria (power: OR = 0.37, 95% CI = 0.22-0.63; speed: OR = 0.64, 95% CI = 0.52-0.79) and KCL criteria (power: OR = 0.40, 95% CI = 0.26-0.62; speed: OR = 0.81, 95% CI = 0.69-0.96) at baseline. Receiver operating characteristic analyses revealed that the area under the curve values of power and speed scores for discriminating mCHS-defined frailty were 0.72 and 0.73. The Cox regression analysis showed that the speed score predicted the incidence of mCHS-defined (HR = 0.45, 95% CI = 0.22-0.92, P = 0.029) and KCL-defined (HR = 0.77, 95% CI = 0.60-0.99, P = 0.039) frailty, whereas the power score was associated with the incidence of KCL-defined frailty (HR = 0.72, 95% CI = 0.55-0.95, P = 0.02) after adjusting for covariates.

The speed and power scores measured during sit-to-stand motion are predictive of frailty in older adults with cardiometabolic disease. Therefore, the GRF parameters measured during sit-to-stand motion could be an important indicator of frailty. Further studies are necessary to examine whether the GRF parameters can be improved by exercise or whether the changes in these parameters are associated with the improvement of frailty status.

Sarcopenia is the loss of muscle strength, mass, and function, which is often exacerbated by chronic comorbidities including cardiovascular diseases, chronic kidney disease, and cancer. Sarcopenia is associated with faster progression of cardiovascular diseases and higher risk of mortality, falls, and reduced quality of life, particularly among older adults. Although the pathophysiologic mechanisms are complex, the broad underlying cause of sarcopenia includes an imbalance between anabolic and catabolic muscle homeostasis with or without neuronal degeneration. The intrinsic molecular mechanisms of aging, chronic illness, malnutrition, and immobility are associated with the development of sarcopenia. Screening and testing for sarcopenia may be particularly important among those with chronic disease states. Early recognition of sarcopenia is important because it can provide an opportunity for interventions to reverse or delay the progression of muscle disorder, which may ultimately impact cardiovascular outcomes. Relying on body mass index is not useful for screening because many patients will have sarcopenic obesity, a particularly important phenotype among older cardiac patients. In this review, we aimed to: (1) provide a definition of sarcopenia within the context of muscle wasting disorders; (2) summarize the associations between sarcopenia and different cardiovascular diseases; (3) highlight an approach for a diagnostic evaluation; (4) discuss management strategies for sarcopenia; and (5) outline key gaps in knowledge with implications for the future of the field.

Joint quasi-stiffness has been often used to inform exoskeleton design. Further understanding of hip quasi-stiffness is needed to design hip exoskeletons. Of interest are wearer responses to walking speed changes with added mass of the exoskeleton. This study analyzed hip quasi-stiffness at 3 walking speed levels and 9 added mass distributions among 13 young and 16 middle-aged adults during mid-stance hip extension and late-stance hip flexion. Compared to young adults, middle-aged adults maintained a higher quasi-stiffness with a smaller range. For a faster walking speed, both age groups increased extension and flexion quasi-stiffness. With mass evenly distributed on the pelvis and thighs or biased to the pelvis, both groups maintained or increased extension quasi-stiffness. With mass biased to the thighs, middle-aged adults maintained or decreased extension quasi-stiffness while young adults increased it. Young adults decreased flexion quasi-stiffness with added mass but not in any generalizable pattern with mass amounts or distributions. Conversely, middle-aged adults maintained or decreased flexion quasi-stiffness with even distribution on the pelvis and thighs or biased to the pelvis, while no change occurred if biased to the thighs. In conclusion, these results can guide the design of a hip exoskeleton's size and mass distribution according to the intended user's age.

Age-related deficits in skeletal muscle function, termed sarcopenia, are due to loss of muscle mass and changes in the intrinsic mechanisms underlying contraction. Sarcopenia is associated with falls, functional decline, and mortality. Electrical impedance myography (EIM)-a minimally invasive, rapid electrophysiological tool-can be applied to animals and humans to monitor muscle health, thereby serving as a biomarker in both preclinical and clinical studies. EIM has been successfully employed in several species; however, the application of EIM to the assessment of zebrafish-a model organism amenable to high-throughput experimentation-has not been reported. Here, we demonstrated differences in EIM measures between the skeletal muscles of young (6 months of age) and aged (33 months of age) zebrafish. For example, EIM phase angle and reactance at 2 kHz showed significantly decreased phase angle (5.3 ± 2.1 versus 10.7 ± 1.5°; p = 0.001) and reactance (89.0 ± 3.9 versus 172.2 ± 54.8 ohms; p = 0.007) in aged versus young animals. Total muscle area, in addition to other morphometric features, was also strongly correlated to EIM 2 kHz phase angle across both groups (r = 0.7133, p = 0.01). Moreover, there was a strong correlation between 2 kHz phase angle and established metrics of zebrafish swimming performance, including turn angle, angular velocity, and lateral motion (r = 0.7253, r = 0.7308, r = 0.7857, respectively, p < 0.01 for all). In addition, the technique was shown to have high reproducibility between repeated measurements with a mean percentage difference of 5.34 ± 1.17% for phase angle. These relationships were also confirmed in a separate replication cohort. Together, these findings establish EIM as a fast, sensitive method for quantifying zebrafish muscle function and quality. Moreover, identifying the abnormalities in the bioelectrical properties of sarcopenic zebrafish provides new opportunities to evaluate potential therapeutics for age-related neuromuscular disorders and to interrogate the disease mechanisms of muscle degeneration.