Cancer Therapy and Exercise Intolerance: The Heart Is But a Part: JACC: CardioOncology State-of-the-Art Review.

The landscape of cancer therapeutics is continually evolving, with successes in improved survivorship and reduced disease progression for many patients with cancer. Improved cancer outcomes expose competing comorbidities, some of which may be exacerbated by cancer therapies. The leading cause of disability and death for many early-stage cancers is cardiovascular disease (CVD), which is often attributed to direct or indirect cardiac injury from cancer therapy. In this review, the authors propose that toxicities related to conventional and novel cancer therapeutics should be considered beyond the heart. The authors provide a framework using the oxygen pathway to understand the impact of cancer treatment on peak oxygen uptake, a marker of integrative cardiopulmonary function and CVD risk. Peripheral toxicities and the impact on oxygen transport are discussed. Consideration for the broad effects of cancer therapies will improve the prediction and identification of cancer survivors at risk for CVD, functional disability, and premature mortality and those who would benefit from therapeutic intervention, ultimately improving patient outcomes.

30-sit-to-stand power is a better tool than isometric knee extensor strength to detect motor impairment in people with haemophilic arthropathy.

INTRODUCTION: Regular assessment of motor impairments is crucial in people with haemophilic arthropathy (PwHA). This study aimed to determine if there are differences in 30-seconds sit-to-stand (30-STS) power and maximal voluntary isometric contraction (MVIC) of the knee extensors between PwHA and healthy control group (CG). The secondary aims were to investigate the correlation between 30-STS power and MVIC of knee extensors with clinical characteristics and to assess their effectiveness in identifying motor impairment in PwHA. METHODS: A cross-sectional study was conducted by collecting data from PwHA (n = 17) and a sedentary CG (n = 15). MVIC (torque) and 30-STS power were normalised to body mass. Correlation analysis and simple linear regression adjusted for age were used to assess the association between tests and clinical variables. Using z-scores derived from the mean and standard deviation of the CG, we compared the MVIC and the 30-STS power in PwHA. RESULTS: PwHA showed lower MVIC and 30-STS power compared to CG (p < .001; large effect size d > .8). Lower 30-STS power was associated with greater joint impairment and greater fear of movement, whereas MVIC showed no association with clinical variables. 30-STS power showed a lower z-score compared to MVIC (p < .001). In addition, 30-STS power detected 47% of PwHA with motor impairment compared to 0% for MVIC (p = .002). CONCLUSIONS: Our results suggest that 30-STS power may be more effective than knee extensors MVIC in detecting motor impairment in PwHA. Consequently, lower limb skeletal muscle power, rather than maximum knee extensor strength, appears to be more affected in PwHA.

Optimization of mHealth behavioral interventions for patients with chronic lymphocytic leukemia: the HEALTH4CLL study.

PURPOSE: This pilot study of a diet and physical activity intervention (HEALTH4CLL) was conducted to reduce fatigue and improve physical function (PF) in patients with chronic lymphocytic leukemia (CLL). METHODS: The HEALTH4CLL study used a randomized factorial design based on the multiphase optimization strategy (MOST). Patients received diet, exercise, and body weight management instructional materials plus a Fitbit and were randomized to undergo one of 16 combinations of 4 evidence-based mHealth intervention strategies over 16 weeks. Patients' fatigue, PF, health-related quality of life, behavior changes, and program satisfaction and retention were assessed. Paired t-tests were used to examine changes in outcomes from baseline to follow-up among patients. Factorial analysis of variance examined effective intervention components and their combinations regarding improvement in fatigue and PF scores. RESULTS: Among 31 patients, we observed significant improvements in fatigue (+ 11.8; t = 4.08, p = 0.001) and PF (+ 2.6; t = 2.75, p = 0.01) scores. The combination of resistance and aerobic exercise with daily self-monitoring was associated with improved fatigue scores (ß = 3.857, SE = 1.617, p = 0.027). Analysis of the individual components of the MOST design demonstrated greater improvement in the PF score with resistance plus aerobic exercise than with aerobic exercise alone (ß = 2.257, SE = 1.071, p = 0.048). CONCLUSIONS: Combined aerobic and resistance exercise and daily self-monitoring improved PF and reduced fatigue in patients with CLL. IMPLICATIONS FOR CANCER SURVIVORS: This pilot study supported the feasibility of a low-touch mHealth intervention for survivors of CLL and provided preliminary evidence that exercising, particularly resistance exercise, can improve their symptoms and quality of life.

Electromyogram Power Spectrum and Cardiac Function Changes After Combined Aerobic Interval Training and Inspiratory Muscle Training in Chronic Heart Failure Patients.

Exercise intolerance and dyspnea are the major symptoms of patients with chronic heart failure (CHF) and are associated with a poor quality of life. In addition to impaired central hemodynamics, symptoms may be attributed to changes in peripheral skeletal muscles. This study aimed to evaluate the effects of aerobic interval training (AIT) combined with inspiratory muscle training (IMT) on cardiac and skeletal muscle function and on functional capacity and dyspnea in patients with CHF and inspiratory muscle weakness.Left ventricle ejection fraction was improved significantly after AIT and AIT & IMT with a high percentage of amelioration (17%, P < 0.042) in the combined group compared to the control group. Therefore, we showed a significant improvement in maximal voluntary isometric force, isometric endurance time, root mean square, and frequency median in both strength and endurance manipulations in the aerobic and combined group; however, the improvement was superior in the combined group compared to the control group. Significant amelioration was proved in functional capacity and dyspnea after all types of training but was performed at 18% higher in 6 minutes' walk test and 43% lower in dyspnea for the combined group compared to the control group.Combining AIT to IMT had optimized exercise training benefits in reversing the cardiac remodeling process and improving skeletal muscle function, functional capacity, and dyspnea in patients with CHF.

Muscle quality, physical performance, and comorbidity are predicted by circulating procollagen type III N-terminal peptide (P3NP): the InCHIANTI follow-up study.

Sarcopenia is characterized by skeletal muscle quantitative and qualitative alterations. A marker of collagen turnover, procollagen type III N-terminal peptide (P3NP), seems to be related to those conditions. This study aims to assess the predictive role of P3NP in muscle density and physical performance changes. In the InCHIANTI study, a representative sample from the registry lists of two towns in Tuscany, Italy, was recruited. Baseline data was collected in 1998, and follow-up visits were conducted every 3 years. Out of the 1453 participants enrolled at baseline, this study includes 1052 participants. According to P3NP median levels, population was clustered in two groups; 544 (51.7%) of the 1052 subjects included were classified in the low median levels (LM-P3NP); at the baseline, they were younger, had higher muscle density, and performed better at the Short Physical Performance Battery (SPPB), compared to the high-median group (HM-P3NP).LM-P3NP cases showed a lower risk to develop liver chronic diseases, CHF, myocardial infarction, and osteoarthritis. HM-P3NP levels were associated with a longitudinal reduction of muscle density, and this effect was potentiated by the interaction between P3NP and leptin. Moreover, variation in physical performance was inversely associated with high level of P3NP, and directly associated with high fat mass, and with the interaction between P3NP and muscle density. Our data indicate that P3NP is associated with the aging process, affecting body composition, physical performance, and clinical manifestations of chronic degenerative age-related diseases.

How does joint impairment affect the functional capacity of the lower limb in early haemophilia-related arthropathy?

INTRODUCTION: The impact of joint damage on functional capacity in patients with mild haemophilia (PwMH) has yet to be well studied. The primary aim of this study was to investigate the effect of joint impairment on the functional capacity of the lower limb in PwMH. The secondary aim was to identify physical predictors of lower limb functional capacity. METHOD: Forty-nine PwMH were evaluated. Dynamic balance was assessed using Time Up and Go (TUG). Thirty-second sit-to-stand (30-STS) and 60-second-STS (60-STS) were used to assess muscle power and endurance, respectively. Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) was used to assess joint damage. PwMH were divided based on HEAD-US: with joint damage (≥3 points) and without or with very low joint damage (0-2 points). Univariate ANOVA and multiple regression analyses were performed to identify differences in functional capacity and potential physical predictors. RESULTS: Only 30-STS showed significant differences between groups (p = .002). TUG and 60-STS were primarily explained by age (r2  = .21 and r2  = .44, respectively), while for 30-STS, age combined with joint damage and pain level explains 54% of the variance. CONCLUSION: Our findings indicate that the 30-STS is useful for assessing functional deterioration in people with early-stage haemophilia-related arthropathy. Our results also indicate that joint damage, combined with ageing and pain, may impact 30-STS outcomes in PwMH. Furthermore, our findings show that the loss in TUG and 60-STS performance in PwMH is related to ageing.

Oat bran prevents high-fat-diet induced muscular dysfunction, systemic inflammation and oxidative stress through reconstructing gut microbiome and circulating metabolome.

Western-type diet characterized by high fat emerges a promoter of skeletal muscle dysfunctions. Oat bran was typically considered a healthy food of premium quality for its abundant dietary fiber. The present study comprehensively explored the effects of a diet rich in oat bran on skeletal muscle disfunctions in high-fat diet (HFD) fed mice. Dietary-fiber-rich oat bran significantly ameliorated HFD-induced skeletal muscle function abnormalities, as evidenced by a phenotype improvement in mice grip strength and endurance treadmill running distance, accompanied with the regulation of muscle functions related gene expressions, namely Fis1, Cytc, Mhy2 and Mhy4. Oat bran suppressed the production of systemic inflammatory cytokines while promoted superoxide dismutase and glutathione. Furthermore, oat bran significantly impacted gut microbiota composition by promoting short chain fatty acids (SCFAs) producers and certain probiotic genera, along with the enhancement of SCFAs. Oat bran also significantly decreased the circulating levels of inflammation-related metabolites and played roles in MAPK signaling, thereafter influencing skeletal muscle functions. Collectively, benefits from integration of biomedical indicators, microbiomics, and metabolomics demonstrates the benefits of oat bran consumption on prevention of HFD-related muscular dysfunctions via alleviating HFD-induced inflammation, gut dysbiosis, and systemic metabolism, pinpointing a novel mechanism underlying the muscle-promoting property of oat bran.

Nonsurgical hypoparathyroidism is associated with skeletal muscle dysfunction and restrictive lung disease.

CONTEXT: Systematic assessment of skeletal muscle function is lacking in patients with nonsurgical hypoparathyroidism (HP). Whether muscle dysfunction involves respiratory muscles and results in restrictive lung disease (RLD) is not studied. OBJECTIVE: To assess skeletal muscle and pulmonary functions in patients with HP. DESIGN: Observational case-control study. METHODS: Thirty patients with HP (mean age 37.7 years, 60% males) and 40 age-, sex-, and body mass index (BMI)-matched healthy controls were assessed for skeletal muscle function by handgrip strength, the short physical performance battery (SPPB) test, dual-energy X-ray absorptiometry (DXA), and electromyography (EMG). Pulmonary function was assessed by spirometry, body plethysmography, diffusion lung capacity for carbon monoxide, and diaphragmatic ultrasound (DUS). RESULTS: Patients with HP had lower serum calcium (2.25 ± 0.15 vs 2.4 ± 0.12 mmol/L, P < .001), serum magnesium (median [interquartile range] 0.74 [0.69-0.82] vs 0.78 [0.69-0.90] mmol/L, P = .04), handgrip strength (18.08 ± 8.36 vs 22.90 ± 7.77 kg, P = .01), and composite SPPB scores (9.5 [7-10] vs 12 [12-12], P < .001) compared to healthy controls. Electromyographic evidence of myopathy was seen in 23% (5 of 22) of patients with HP but in none of the controls (P = .08). The prevalence of RLD was higher in the HP cohort compared to that in controls (24% vs 0%, P = .01). Diaphragmatic excursion (DE) (4.22 ± 1.38 vs 5.18 ± 1.53 cm, P = .01) and diaphragmatic thickness (DT) (3.79 ± 1.18 vs 4.28 ± 0.94 mm, P = .05) on deep inspiration were reduced in patients with HP. CONCLUSION: Detailed testing of patients with HP without overt muscle and lung diseases revealed significant impairment in parameters of skeletal muscle function. Myopathy and RLD were observed in a considerable proportion of patients with HP.

The Addition of Sprint Interval Training to Field Lacrosse Training Increases Rate of Torque Development and Contractile Impulse in Female High School Field Lacrosse Players.

Field lacrosse requires sudden directional changes and rapid acceleration/deceleration. The capacity to perform these skills is dependent on explosive muscle force production. Limited research exists on the potential of sprint interval training (SIT) to impact explosive muscle force production in field lacrosse players. The purpose of this study is to examine SIT, concurrent to field-lacrosse-specific training, on the rate of torque development (RTD), contractile impulse, and muscle function in female high school field lacrosse players (n = 12; 16 ± 1 yrs.). SIT was performed three times per week, concurrent to field-lacrosse-specific training, for 12 weeks. Right lower-limb muscle performance was assessed pre-, mid-, and post-SIT training via isometric and isokinetic concentric knee extensor contractions. Outcomes included RTD (Nm·s-1), contractile impulse (Nm·s), and peak torque (Nm). RTD for the first 50 ms of contraction improved by 42% by midseason and remained elevated at postseason (p = 0.004, effect size (ES) = -577.3 to 66.5). Contractile impulse demonstrated a training effect across 0-50 ms (42%, p = 0.004, ES = -1.4 to 0.4), 0-100 ms (33%, p = 0.018, ES = 3.1 to 0.9), and 0-200 ms (22%, p = 0.031, ES = -7.8 to 1.6). Isometric (0 rad·s-1) and concentric (3.1 rad·s-1) strength increased by 20% (p = 0.002, ES = -60.8 to -20.8) and 9% (p = 0.038, ES = -18.2 to 0.0) from SIT and field-lacrosse-specific training, respectively (p < 0.05). SIT, concurrent to field-lacrosse-specific training, enhanced lower-limb skeletal muscle performance, which may enable greater sport-specific gains.

A potential correlation between adipokines, skeletal muscle function and bone mineral density in middle-aged and elderly individuals.

BACKGROUND: Evidence exists of a strong association between inflammation and a decrease in skeletal muscle function and bone mineral density (BMD); however, the specific mechanisms of these associations remain unclear. Adipokines, as key regulators of the inflammatory response, may be implicated in these processes. The objective of this study was to explore the potential correlation between adipokines, skeletal muscle function and BMD in middle-aged and elderly individuals. METHODS: A comparative cross-sectional study was carried out at the Huadong Hospital Affiliated with Fudan University (Shanghai, China). A total of 460 middle-aged and elderly individuals were recruited, and 125 were enrolled in the analysis. Their biochemical indices, body composition, skeletal muscle function and BMD were measured. Bioinformatic analysis was also employed to identify potential adipokine targets linked to skeletal muscle function and BMD. To validate these targets, plasma and peripheral blood mononuclear cells (PBMCs) were harvested from these individuals and subjected to western blotting (WB) and enzyme-linked immunosorbent assay (ELISA). RESULTS: Individuals in this cross-sectional study were categorized into 2 groups according to their median skeletal muscle mass (SMM) (28.8 kg for males and 20.6 kg for females). Individuals with lower SMM exhibited poorer grip strength (P = 0.017), longer 5-Times-Sit-to-Stand Test (FTSST) duration (P = 0.029), lower total hip BMD (P = 0.043), lower femoral neck BMD (P = 0.011) and higher levels of inflammatory markers in comparison with individuals with higher SMM. Bioinformatics analysis identified LEP, ADIPOQ, RBP4, and DPP4 as potential adipokine targets associated with skeletal muscle function and BMD. In vitro experiments demonstrated that individuals with decreased skeletal muscle function and BMD expressed higher levels of these adipokines. CONCLUSIONS: Skeletal muscle function is positively correlated with BMD and negatively correlated with levels of inflammatory markers among middle-aged and elderly individuals. Those with lower skeletal muscle function and BMD tend to have a higher expression of LEP, ADIPOQ, RBP4 and DPP4.

Regulation of mitochondrial morphology and cristae architecture by the TLR4 pathway in human skeletal muscle.

In skeletal muscle (SkM), a reduced mitochondrial elongate phenotype is associated with several metabolic disorders like type 2 diabetes mellitus (T2DM). However, the mechanisms contributing to this reduction in mitochondrial elongate phenotype in SkM have not been fully elucidated. It has recently been shown in a SkM cell line that toll-like receptor 4 (TLR4) contributes to the regulation of mitochondrial morphology. However, this has not been investigated in human SkM. Here we found that in human SkM biopsies, TLR4 protein correlated negatively with Opa1 (pro-mitochondrial fusion protein). Moreover, the incubation of human myotubes with LPS reduced mitochondrial size and elongation and induced abnormal mitochondrial cristae, which was prevented with the co-incubation of LPS with TAK242. Finally, T2DM myotubes were found to have reduced mitochondrial elongation and mitochondrial cristae density. Mitochondrial morphology, membrane structure, and insulin-stimulated glucose uptake were restored to healthy levels in T2DM myotubes treated with TAK242. In conclusion, mitochondrial morphology and mitochondrial cristae seem to be regulated by the TLR4 pathway in human SkM. Those mitochondrial alterations might potentially contribute to insulin resistance in the SkM of patients with T2DM.

Neuromuscular junction transmission failure in aging and sarcopenia: The nexus of the neurological and muscular systems.

Sarcopenia, or age-related decline in muscle form and function, exerts high personal, societal, and economic burdens when untreated. Integrity and function of the neuromuscular junction (NMJ), as the nexus between the nervous and muscular systems, is critical for input and dependable neural control of muscle force generation. As such, the NMJ has long been a site of keen interest in the context of skeletal muscle function deficits during aging and in the context of sarcopenia. Historically, changes of NMJ morphology during aging have been investigated extensively but primarily in aged rodent models. Aged rodents have consistently shown features of NMJ endplate fragmentation and denervation. Yet, the presence of NMJ changes in older humans remains controversial, and conflicting findings have been reported. This review article describes the physiological processes involved in NMJ transmission, discusses the evidence that supports NMJ transmission failure as a possible contributor to sarcopenia, and speculates on the potential of targeting these defects for therapeutic development. The technical approaches that are available for assessment of NMJ transmission, whether each approach has been applied in the context of aging and sarcopenia, and the associated findings are summarized. Like morphological studies, age-related NMJ transmission deficits have primarily been studied in rodents. In preclinical studies, isolated synaptic electrophysiology recordings of endplate currents or potentials have been mostly used, and paradoxically, have shown enhancement, rather than failure, with aging. Yet, in vivo assessment of single muscle fiber action potential generation using single fiber electromyography and nerve-stimulated muscle force measurements show evidence of NMJ failure in aged mice and rats. Together these findings suggest that endplate response enhancement may be a compensatory response to post-synaptic mechanisms of NMJ transmission failure in aged rodents. Possible, but underexplored, mechanisms of this failure are discussed including the simplification of post-synaptic folding and altered voltage-gated sodium channel clustering or function. In humans, there is limited clinical data that has selectively investigated single synaptic function in the context of aging. If sarcopenic older adults turn out to exhibit notable impairments in NMJ transmission (this has yet to be examined but based on available evidence appears to be plausible) then these NMJ transmission defects present a well-defined biological mechanism and offer a well-defined pathway for clinical implementation. Investigation of small molecules that are currently available clinically or being testing clinically in other disorders may provide a rapid route for development of interventions for older adults impacted by sarcopenia.

Synergistic Strategies to Accelerate the Development of Function-Promoting Therapies: Lessons From Operation Warp Speed and Oncology Drug Development.

BACKGROUND: Functional limitations and physical disabilities associated with aging and chronic disease are major concerns for human societies and expeditious development of function-promoting therapies is a public health priority. METHODS: Expert panel discussion. RESULTS: The remarkable success of Operation Warp Speed for the rapid development of COVID-19 vaccines, COVID-19 therapeutics, and of oncology drug development programs over the past decade have taught us that complex public health problems such as the development of function-promoting therapies will require collaboration among many stakeholders, including academic investigators, the National Institutes of Health, professional societies, patients and patient advocacy organizations, the pharmaceutical and biotechnology industry, and the U.S. Food and Drug Administration. CONCLUSIONS: There was agreement that the success of well designed, adequately powered clinical trials will require careful definitions of indication/s, study population, and patient-important endpoints that can be reliably measured using validated instruments, commensurate resource allocation, and versatile organizational structures such as those used in Operation Warp Speed.

Muscle Quality in Older Adults: A Scoping Review.

OBJECTIVE: This scoping review aimed to map out currently available definitions and assessment methods of muscle quality in older adults. DESIGN: Scoping review. SETTING AND PARTICIPANTS: All available studies. METHODS: Four databases (PubMed, EMBASE, Web of Science, and Cochrane Library) were searched from inception to May 2022. Title, abstract, and full-text screening were undertaken by 2 reviewers independently. Observational and experimental studies were eligible for inclusion if there was a clear description of muscle quality assessment in individuals aged 60+ years. RESULTS: A total of 96 articles were included. Several definitions and assessment methods of muscle quality were identified and divided into 2 main domains: (1) functional domain, and (2) morphological domain. A total of 70% and 30% of the included studies assessed muscle quality in the functional and morphological domains, respectively. In the functional domain, most studies defined muscle quality as the ratio of knee extension strength by leg lean mass (45.9%). In the morphological domain, most studies defined muscle quality as the echo intensity of quadriceps femoris by ultrasound (50.0%). CONCLUSIONS AND IMPLICATIONS: There is a substantial heterogeneity of definitions and assessment methods of muscle quality in older adults. Herein, we propose a standardized definition of muscle quality to include terminology, domain, and assessment methods (tests, tools, and body sites). Such standardization may help researchers, clinicians, and decision makers use muscle quality as a potential marker of "skeletal muscle health" in older adults.

Is dexamethasone-induced muscle atrophy an alternative model for naturally aged sarcopenia model?

Background: Primary sarcopenia is usually known as age-related skeletal muscle loss; however, other factors like endocrine, lifestyle and inflammation can also cause muscle loss, known as secondary sarcopenia. Although many studies have used different sarcopenia animal models for exploring the underlying mechanism and therapeutic approaches for sarcopenia, limited study has provided evidence of the relevance of these animal models. This study aims to investigate the similarity and difference in muscle qualities between primary and secondary sarcopenia mice models, using naturally aged mice and dexamethasone-induced mice. Methods: 21-month-old mice were used as naturally aged primary sarcopenia mice and 3-month-old mice received daily intraperitoneal injection of dexamethasone (20 mg/ kg body weight) for 10 days were used as secondary sarcopenia model. This study provided measurements for muscle mass and functions, including Dual-energy X-ray absorptiometry (DXA) scanning, handgrip strength test and treadmill running to exhaustion test. Besides, muscle contraction, muscle fibre type measurements and gene expression were also performed to provide additional information on muscle qualities. Results: The results suggest two sarcopenia animal models shared a comparable decrease in forelimb lean mass, muscle fibre size, grip strength and muscle contraction ability. Besides, the upregulation of protein degradation genes was also observed in two sarcopenia animal models. However, only primary sarcopenia mice were identified with an early stage of mtDNA deletion. Conclusion: Collectively, this study evaluated that the dexamethasone-induced mouse model could be served as an alternative model for primary sarcopenia, according to the comparable muscle mass and functional changes. However, whether dexamethasone-induced mice can be used as an animal model when studying the molecular mechanisms of sarcopenia needs to be carefully evaluated. The translational potential of this article: The purpose of sarcopenia research is to investigate appropriate treatments for reversing the loss of skeletal muscle mass and functions. Using animal models for the preclinical study could predict the safety and efficacy of the treatments. This study compared the typical age-related sarcopenia mice model and dexamethasone-induced secondary sarcopenia mice to provide evidence of the pathological and functional changes in the mice models.

Effects of hydroxyurea on skeletal muscle energetics and force production in a sickle cell disease murine model.

Hydroxyurea (HU) is commonly used as a treatment for patients with sickle cell disease (SCD) to enhance fetal hemoglobin production. This increased production is expected to reduce anemia (which depresses oxygen transport) and abnormal Hb content alleviating clinical symptoms such as vaso-occlusive crisis and acute chest syndrome. The effects of HU on skeletal muscle bioenergetics in vivo are still unknown. Due to the beneficial effects of HU upon oxygen delivery, improved skeletal muscle energetics and function in response to a HU treatment have been hypothesized. Muscle energetics and function were analyzed during a standardized rest-exercise-recovery protocol, using 31P-magnetic resonance spectroscopy in Townes SCD mice. Measurements were performed in three groups of mice: one group of 2-mo-old mice (SCD2m, n = 8), another one of 4-mo-old mice (SCD4m, n = 8), and a last group of 4-mo-old mice that have been treated from 2 mo of age with HU at 50 mg/kg/day (SCD4m-HU, n = 8). As compared with SCD2m mice, SCD4m mice were heavier and displayed a lower acidosis. As lower specific forces were developed by SCD4m compared with SCD2m, greater force-normalized phosphocreatine consumption and oxidative and nonoxidative costs of contraction were also reported. HU-treated mice (SCD4m-HU) displayed a significantly higher specific force production as compared with untreated mice (SCD4m), whereas muscle energetics was unchanged. Overall, our results support a beneficial effect of HU on muscle function.NEW & NOTEWORTHY Our results highlighted that force production decreases between 2 and 4 mo of age in SCD mice thereby indicating a decrease of muscle function during this period. Of interest, HU treatment seemed to blunt the observed age effect given that SCD4m-HU mice displayed a higher specific force production as compared with SCD4m mice. In that respect, HU treatment would help to maintain a higher capacity of force production during aging in SCD.

[A new screening method for the diagnosis of sarcopenia in people 65 years and older.]

Diagnosis of sarcopenia is difficult due to the limitations of measuring muscle mass, which requires specialized equipment. Simple screening tools can be useful in general practice. The aim of the study was to develop a new screening method for diagnosing sarcopenia based on risk factors and biomarkers of the disease. The study included 230 people over 65 years and older (70 men and 160 women, median age 75 [68; 79] years) examined in a medical institution in St. Petersburg. Sarcopenia was diagnosed according to the updated consensus of the European Working Group on Sarcopenia 2 (EWGSOP2, 2018). When constructing a mathematical model, such indicators as the number of falls, BMI, fatigue, and the level of C-reactive protein in the blood serum had the greatest diagnostic significance of sarcopenia. The calculations showed high sensitivity - 91,4%, specificity - 88,7% and accuracy - 89,9% of the screening method for diagnosing sarcopenia in people 65 years and older.

Public Health Need, Molecular Targets, and Opportunities for the Accelerated Development of Function-Promoting Therapies: Proceedings of a National Institute on Aging Workshop.

BACKGROUND: People ≥ 65 years are expected to live a substantial portion of their remaining lives with a limiting physical condition and the numbers of affected individuals will increase substantially due to the growth of the population of older adults worldwide. The age-related loss of muscle mass, strength, and function is associated with an increased risk of physical disabilities, falls, loss of independence, metabolic disorders, and mortality. The development of function-promoting therapies to prevent and treat age-related skeletal muscle functional limitations is a pressing public health problem. METHODS: On March 20-22, 2022, the National Institute on Aging (NIA) held a workshop entitled "Development of Function-Promoting Therapies: Public Health Need, Molecular Targets, and Drug Development." RESULTS: The workshop covered a variety of topics including advances in muscle biology, novel candidate molecules, findings from randomized trials, and challenges in the design of clinical trials and regulatory approval of function-promoting therapies. Leading academic investigators, representatives from the National Institutes of Health (NIH) and the U.S. Food and Drug Administration (FDA), professional societies, pharmaceutical industry, and patient advocacy organizations shared research findings and identified research gaps and strategies to advance the development of function-promoting therapies. A diverse audience of 397 national and international professionals attended the conference. CONCLUSIONS: Function-promoting therapies to prevent and treat physical disabilities associated with aging and chronic diseases are a public health imperative. Appropriately powered, well-designed clinical trials and synergistic collaboration among academic experts, patients and stakeholders, the NIH and the FDA, and the pharmaceutical industry are needed to accelerate the development of function-promoting therapies.

Bioactive Components in Whole Grains for the Regulation of Skeletal Muscle Function.

Skeletal muscle plays a primary role in metabolic health and physical performance. Conversely, skeletal muscle dysfunctions such as muscular dystrophy, atrophy and aging-related sarcopenia could lead to frailty, decreased independence and increased risk of hospitalization. Dietary intervention has become an effective approach to improving muscle health and function. Evidence shows that whole grains possess multiple health benefits compared with refined grains. Importantly, there is growing evidence demonstrating that bioactive substances derived from whole grains such as polyphenols, γ-oryzanol, ß-sitosterol, betaine, octacosanol, alkylresorcinols and ß-glucan could contribute to enhancing myogenesis, muscle mass and metabolic function. In this review, we discuss the potential role of whole-grain-derived bioactive components in the regulation of muscle function, emphasizing the underlying mechanisms by which these compounds regulate muscle biology. This work will contribute toward increasing awareness of nutraceutical supplementation of whole grain functional ingredients for the prevention and treatment of muscle dysfunctions.