Decline In Muscle Mass Research Articles

Integrating Mechanisms of Exacerbated Atrophy and Other Adverse Skeletal Muscle Impact in COPD.

The normal decline in skeletal muscle mass that occurs with aging is exacerbated in patients with chronic obstructive pulmonary disease (COPD) and contributes to poor health outcomes, including a greater risk of death. There has been controversy about the causes of this exacerbated muscle atrophy, with considerable debate about the degree to which it reflects the very sedentary nature of COPD patients vs. being precipitated by various aspects of the COPD pathophysiology and its most frequent proximate cause, long-term smoking. Consistent with the latter view, recent evidence suggests that exacerbated aging muscle loss with COPD is likely initiated by decades of smoking-induced stress on the neuromuscular junction that predisposes patients to premature failure of muscle reinnervation capacity, accompanied by various alterations in mitochondrial function. Superimposed upon this are various aspects of COPD pathophysiology, such as hypercapnia, hypoxia, and inflammation, that can also contribute to muscle atrophy. This review will summarize the available knowledge concerning the mechanisms contributing to exacerbated aging muscle affect in COPD, consider the potential role of comorbidities using the specific example of chronic kidney disease, and identify emerging molecular mechanisms of muscle impairment, including mitochondrial permeability transition as a mechanism of muscle atrophy, and chronic activation of the aryl hydrocarbon receptor in driving COPD muscle pathophysiology.

Human skeletal muscle acetylcholine receptor gene expression in elderly males performing heavy resistance exercise.

Muscle fiber denervation is a major contributor to the decline in muscle mass and function during aging. Heavy resistance exercise is an effective tool for increasing muscle mass and strength, but whether it can rescue denervated muscle fibers remains unclear. Therefore, the purpose of this study was to investigate the potential of heavy resistance exercise to modify indices of denervation in healthy elderly individuals. Thirty-eight healthy elderly men (72 ± 5 yr) underwent 16 wk of heavy resistance exercise, whereas 20 healthy elderly men (72 ± 6 yr) served as nonexercising sedentary controls. Muscle biopsies were obtained pre and post training, and midway at 8 wk. Biopsies were analyzed by immunofluorescence for the prevalence of myofibers expressing embryonic myosin [embryonic myosin heavy chain (MyHCe)], neonatal myosin [neonatal myosin heavy chain (MyHCn)], nestin, and neural cell adhesion molecule (NCAM), and by RT-qPCR for gene expression levels of acetylcholine receptor (AChR) subunits, MyHCn, MyHCe, p16, and Ki67. In addition to increases in strength and type II fiber hypertrophy, heavy resistance exercise training led to a decrease in AChR α1 and ε subunit messenger RNA (mRNA; at 8 wk). Changes in gene expression levels of the α1 and ε AChR subunits with 8 wk of heavy resistance exercise supports the role of this type of exercise in targeting stability of the neuromuscular junction. The number of fibers positive for NCAM, nestin, and MyHCn was not affected, suggesting that a longer timeframe is needed for adaptations to manifest at the protein level.

Association Between C-Reactive Protein and Relative Handgrip Strength in Postmenopausal Korean Women Aged 45-80 Years: A Cross-Sectional Study.

BackgroundChronic inflammation plays a key role in the pathophysiology of frailty and loss of physical performance, which are closely associated with sarcopenia. In women, the decline in muscle mass and strength is accelerated after menopause. Thus, we examined the association between high sensitivity C-reactive protein (hs-CRP) and relative handgrip strength (HGS) in postmenopausal women.MethodsThis cross-sectional study included 2171 postmenopausal women aged ≥45 years who participated in the Korean National Health and Nutrition Survey (KNHNES) between 2015 and 2018. Relative HGS was categorized into quartiles as follows: Q1, <0.810 (kg/BMI); Q2, 0.810–0.968 (kg/BMI); Q3, 0.969–1.119 (kg/BMI); Q4, >1.119 (kg/BMI). The odds ratios (ORs) and 95% confidence intervals (95% CIs) for high hs-CRP (>1.0 mg/L, 75 percentile of the current samples) were calculated across relative HGS quartiles using multiple logistic regression analysis.ResultsThe prevalence of high hs-CRP decreased with relative HGS quartiles. Compared to the highest quartile, the OR (95% CI) of the lowest relative HGS quartile for high hs-CRP was 3.266 (2.227–4.789) after adjusting for age, hypertension, diabetes mellitus, dyslipidemia, education, household income, physical activity, strength exercise, smoking, and alcohol ingestion.ConclusionSerum hs-CRP level was inversely and independently associated with relative HGS. Our findings indicate that low-grade inflammation is inversely associated with muscle strength in postmenopausal women.

Impact of Intermittent Fasting Combined With High-Intensity Interval Training on Body Composition, Metabolic Biomarkers, and Physical Fitness in Women With Obesity.

BackgroundIntermittent fasting (IF) is a dietary approach that is widely popular due to its effects on weight and body fat loss, but it does not appear to ensure muscle mass preservation. Incorporating high-intensity interval training (HIIT) into an individual’s routine could be an attractive and viable therapeutic option for improving body composition, lifestyle and health promotion. Problematizing the emerging situation of fighting obesity, led us to clarify gaps about IF and hypothesize that IF and HIIT in conjunction may protect against muscle mass decline without impairing nitrogen balance (NB), in addition to improving the physical fitness of women with obesity.ObjectivesTo evaluate the effects of IF alone and combined with HIIT on body composition, NB and strength and physical fitness in women with obesity.MethodsThirty-six women (BMI 34.0 ± 3.2; 32.2 ± 4.4 years) participated and were randomly distributed into three groups: (1) Intermittent fasting combined with exercise group (IF + EX); (2) Exercise group (EX); and (3) Intermittent fasting group (IF). The interventions took place over 8 weeks and all evaluations were performed pre and post-intervention. The HIIT circuit was performed 3x/week, for 25 mins/session, at 70–85% of the maximum heart rate. The intermittent fasting protocol was a 5:2 diet with two meals within 6 h on fasting days, being 25% of total energy intake, plus 18 h of complete fasting. The protocol was performed 2x/week and 5 days of ad libitum ingestion. Resting metabolic rate (RMR) was measured by indirect calorimetry, body composition by BodPod®, NB from urinary nitrogen, food consumption by food records and physical and strength performance were measured by physical tests. ANOVA two-way repeated measures mixed model was performed followed by Sidak post hoc (p < 0.05). This project was registered in ClinicalTrials.gov, NCT05237154.ResultsThere were a reduction in body weight (P = 0.012) and BMI (P = 0.031) only in the IF + EX group. There was body fat loss in the IF + EX group (−4%, P < 0.001) and in the EX group (−2.3%, P = 0.043), an increase in fat-free mass in the IF + EX group (+3.3%, P < 0.001) and also in the EX group (+2%, P = 0.043), without differences between groups and the IF group showed no changes. The NB was equilibrium in all groups. All parameters of aerobic capacity and strength improved.ConclusionCombining IF with HIIT can promote increments in fat-free mass, NB equilibrium and improve physical fitness and strength.

Effect of enhanced muscle tone on the expression of atrogenes and cytoskeletal proteins during postural muscle unloading

Skeletal muscle unloading leads to the decreased electrical activity and decline of muscle tone. Aims: Current study evaluated the effect of muscle tone preservation achieved by tetanus toxin (TeNT) treatment on signaling pathways regulating atrophic processes during unloading. Main methods: Four groups of rats were used: non-treated control (C), control rats with TeNT administration (CT), 7 days of unloading/hindlimb suspension with placebo (HS), and 7 days of unloading with TeNT administration (HST). Key findings: Absolute and relative force of tetanic contractions was decreased by 65% in soleus muscle of HS rats when compared with C. Treatment with TeNT significantly lessened force decline in soleus muscle of HST rats when compared with HS. TeNT administration increased myosin heavy chain I beta (MyHC Iβ) expression in CT rats and prevented MyHC Iβ loss in HST group when compared with C rats. Desmin content was lower by 31.4% (p < 0.05) in HS group when compared with HST. Calpain-1 expression was increased in HS group when compared with C, CT and HST. There was a decrease in p-p70S6K content (41%, p < 0,05) and an increase in p-eEF2 content (77%, p < 0,05) in HS group when compared with C, while there were no significant differences in the content of these proteins between HST, CT and C groups. Significance: Treatment with TeNT significantly diminished unloading-induced decline of soleus muscle mass and mechanical properties and affected the regulation of MyHC Iβ expression. These effects are mediated by signaling pathways regulating protein synthesis and degradation.

Nutrition in old age-key to maintaining functionality and quality of life

Jenseits des 70. Lebensjahrs ist bei älteren Menschen regelhaft eine Abnahme der Muskelmasse sowie eine Zunahme der Fettmasse zu beobachten. Diese Veränderungen der Körperzusammensetzung stellen eine wesentliche Prädisposition für den im Alter drohenden Verlust an Funktionalität und Selbstständigkeit dar. In diesem Kontext kommt der richtigen Ernährung sowie insbesondere dem Vermeiden einer Mangelernährung große Relevanz zu. Da die ältere Bevölkerung hinsichtlich der Geschwindigkeit und Ausprägung der Alterungsvorgänge sowie ihrer Komorbiditäten als äußerst heterogen zu betrachten ist, müssen Ernährungsempfehlungen individualisiert erfolgen. In Hinblick auf eine potenzielle Gefährdung durch eine Sarkopenie ist selbst eine beabsichtigte Gewichtsabnahme im Alter kritisch zu sehen. Fastenepisoden sollten generell vermieden werden. Dies betrifft insbesondere eine unzureichende Kalorienzufuhr im Kontext von akuten oder chronischen Erkrankungen. Im höheren Lebensalter sollten daher regelmäßige Gewichtskontrollen erfolgen, um das Auftreten einer Mangelernährung frühzeitig zu erkennen und entsprechende Maßnahmen einleiten zu können. Zum Erhalt der Muskelmasse und -funktion sollte eine gegenüber jüngeren Menschen erhöhte Eiweißzufuhr von 1,0 g/kgKG angestrebt werden. Bei älteren Menschen mit Sarkopenie wird dieses Ziel auf 1,2 g/kg KG angehoben. Während sich im Alter restriktive Diäten als nachteilig erweisen können, scheinen gesunde Ernährungsformen wie z. B. die mediterrane Ernährung den Erhalt der muskulären und kognitiven Funktion zu fördern.

Mitochondrial Uncoupling Decreases Sarcopenic Obesity By Activation of Skeletal Muscle Mitochondrial Quality Control and Attenuated ER Stress

BackgroundSarcopenic obesity is a highly prevalent disease with poor survival and ineffective medical interventions. Mitochondrial dysfunction is purported to be central in the pathogenesis of sarcopenic obesity by impairing both organelle biogenesis and quality control. We have previously identified an orally available mitochondrial‐targeted furazano[3,4‐b]pyrazine named BAM15 that selectively lowers respiratory coupling efficiency and protects against diet‐induced obesity in mice. Here, we tested the hypothesis that mitochondrial uncoupling simultaneously attenuates loss of muscle function and weight gain in a mouse model of sarcopenic obesity.Methods80‐week‐old male C57BL/6J mice with obesity were randomized to 10 weeks of high fat diet (CTRL) or BAM15 (BAM15; 0.1% w/w in high fat diet) treatment. Body composition, muscle function, energy expenditure, and locomotor activity were determined after treatment. Skeletal muscle was harvested and evaluated for histology, gene expression, protein signaling, and mitochondrial structure and function.ResultsBAM15 decreased body weight (~25% reduction, P&lt;0.001) which was attributable to increased energy expenditure (~20% increment, P&lt;0.001). BAM15 increased muscle mass (~13% increment, P&lt;0.001), strength (~37% increment, P&lt;0.0001), and locomotor activity (~25% increment, P&lt;0.001). Improvements in physical function were mediated in part by reductions in skeletal muscle inflammation (IL‐6 and gp130, both P&lt;0.05), enhanced mitochondrial function, and improved endoplasmic reticulum homeostasis and reduced inflammation. Specifically, BAM15 activated mitochondrial quality control through AMPK (PINK1‐ubiquitin binding and LC3II, P&lt;0.01), increased electron transport chain activity (citrate synthase and complex II activity, all P&lt;0.05), restricted endoplasmic reticulum (ER) misfolding (decreased oligomer A11 insoluble/soluble ratio, P&lt;0.0001) while limiting ER stress (decreased PERK signaling, P&lt;0.0001), apoptotic signaling (decreased cytochrome C release and Caspase‐3/9 activation, all P&lt;0.001), and muscle protein degradation (decreased 14‐kDa actin fragment insoluble/soluble ratio, P&lt;0.001).ConclusionsMitochondrial uncoupling agents such as BAM15 may mitigate age‐related decline in muscle mass and function by molecular and cellular bioenergetic adaptations that confer protection against sarcopenic obesity through activation of mitochondrial quality control and attenuation of ER stress.

Modulating Intramuscular Fat Infiltration by Small Molecules

Skeletal muscle has a remarkable ability to regenerate upon injury. However, during aging and in diseases such as muscular dystrophies and diabetes, muscle tissue is replaced by fibrotic scar and fat tissue in a process called fatty fibrosis. Currently, there are no known treatments to prevent fatty fibrosis or the decline in muscle mass and function. Our lab and others have shown that ectopic activation of the Hedgehog (Hh) pathway accelerated muscle regeneration after an acute injury and preserved muscle function with age and disease. In addition, our lab demonstrated that Hh is a potent anti‐adipogenic signal and that activating Hh prevents intramuscular fat formation. However, the cellular and molecular mechanisms by which Hh balances fatty fibrosis and muscle regeneration are unclear. In this project, we use small molecules as a novel approach for modulating intramuscular fat infiltration via Hh signaling: Smoothened agonist (SAG) to activate and Vismodegib to inactivate Hh. We found that SAG (HHON) successfully activates the Hh pathway while Vismodegib (HHOFF) inactivates the pathway, as detected by RT‐qPCR analysis for the expression of key Hh target gene Gli1. Excitingly, by modulating the Hh pathway, SAG and Vismodegib decreased and increased fat infiltration, respectively. We are currently evaluating the effects of SAG and Vismodegib administration on muscle regeneration and fibrosis. Future experiments will focus on using small molecules to modulate the Hh pathway at different time points after injury, as well as looking to therapeutic applications in treating fatty fibrosis in conditions such as Duchenne muscular dystrophy. Together, the results of this project will help uncover the regulatory role and dynamics of Hh signaling in intramuscular fat infiltration, ultimately providing a starting point for developing powerful new therapeutics to treat fatty fibrosis.

Exploring Muscle Health Deterioration and Its Determinants Among Community-Dwelling Older Adults.

BackgroundAge-related muscle mass and function decline are critical issues that have gained attention in clinical practice and research. Nevertheless, little is known regarding the time course of muscle health progression, and its determinants during this transition should be estimated.MethodsWe enrolled community-dwelling adults aged ≥65 years during their regular health checkup. The participants’ body composition and muscle function were measured annually from 2015 to 2021. Presarcopenia was characterized by the loss of muscle mass only; dynapenia was defined as low muscle function without changes in muscle mass; and sarcopenia was indicated as a decline in both muscle mass and muscle function. We observed the natural course of muscle health progression during aging. The relationship between muscle health decline and different determinants among old adults was examined.ResultsAmong 568 participants, there was 18.49%, 3.52%, and 1.06% of healthy individuals transited to dynapenia, presarcopenia, and sarcopenia, respectively. Significant positive correlations between age, fat-to-muscle ratio (FMR) and the dynapenia transition were existed [hazard ratio (HR) = 1.08 and HR = 1.73, all p < 0.05]. Serum albumin level had negative correlation with the dynapenia transition risk (HR = 0.30, p = 0.004). Participants with these three risk factors had the highest HR of dynapenia transition compared to those without (HR = 8.67, p = 0.001). A dose-response effect existed between risk factors numbers and the risk of dynapenia transition (p for trend < 0.001). This positive association and dose-response relationship remains after multiple covariates adjustment (HR = 7.74, p = 0.002, p for trend < 0.001). Participants with two or more than two risk factors had a higher risk of dynapenia transition than those with low risk factors (p = 0.0027), and the HR was 1.96 after multiple covariate adjustment (p = 0.029).ConclusionHealthy community-dwelling old adults tended to transit to dynapenia during muscle health deterioration. Individuals with older age, higher FMR, lower albumin level had a higher risk of dynapenia transition; and a positive dose-response effect existed among this population as well.

Cancer-cell-secreted miR-122 suppresses O-GlcNAcylation to promote skeletal muscle proteolysis.

A decline in skeletal muscle mass and lower muscular strength are prognostic factors in advanced human cancers. Here, we found that breast cancer suppressed O-linked N-acetylglucosamine (O-GlcNAc) protein modification in muscle through extracellular-vesicle-encapsulated miR-122, which targets O-GlcNAc transferase (OGT). Mechanistically, O-GlcNAcylation of the ryanodine receptor 1 (RYR1) competed with NEK10-mediated phosphorylation and increased K48-linked ubiquitination and proteasomal degradation; the miR-122-mediated decrease in OGT resulted in increased RYR1 abundance. We further found that muscular protein O-GlcNAcylation was regulated by hypoxia and lactate through HIF1A-dependent OGT promoter activation and was elevated after exercise. Suppressed O-GlcNAcylation in the setting of cancer, through increasing RYR1, led to higher cytosolic Ca2+ and calpain protease activation, which triggered cleavage of desmin filaments and myofibrillar destruction. This was associated with reduced skeletal muscle mass and contractility in tumour-bearing mice. Our findings link O-GlcNAcylation to muscular protein homeostasis and contractility and reveal a mechanism of cancer-associated muscle dysregulation.

Malnutrition risk and the need for dietetic intervention post COVID-19 infection on a care of the elderly rehab ward

Patients recovering from COVID-19 are at high risk of malnutrition, reduced nutritional intake and decline in muscle mass and strength with many requiring significant rehabilitation. The aim of this service evaluation is to quantify the risk of malnutrition and provide an overview of nutritional status and outcomes with dietetic input on a care of the elderly rehab ward.

Mitochondrial uncoupling attenuates sarcopenic obesity by enhancing skeletal muscle mitophagy and quality control.

BackgroundSarcopenic obesity is a highly prevalent disease with poor survival and ineffective medical interventions. Mitochondrial dysfunction is purported to be central in the pathogenesis of sarcopenic obesity by impairing both organelle biogenesis and quality control. We have previously identified that a mitochondrial‐targeted furazano[3,4‐b]pyrazine named BAM15 is orally available and selectively lowers respiratory coupling efficiency and protects against diet‐induced obesity in mice. Here, we tested the hypothesis that mitochondrial uncoupling simultaneously attenuates loss of muscle function and weight gain in a mouse model of sarcopenic obesity.MethodsEighty‐week‐old male C57BL/6J mice with obesity were randomized to 10 weeks of high fat diet (CTRL) or BAM15 (BAM15; 0.1% w/w in high fat diet) treatment. Body weight and food intake were measured weekly. Body composition, muscle function, energy expenditure, locomotor activity, and glucose tolerance were determined after treatment. Skeletal muscle was harvested and evaluated for histology, gene expression, protein signalling, and mitochondrial structure and function.ResultsBAM15 decreased body weight (54.0 ± 2.0 vs. 42.3 ± 1.3 g, P < 0.001) which was attributable to increased energy expenditure (10.1 ± 0.1 vs. 11.3 ± 0.4 kcal/day, P < 0.001). BAM15 increased muscle mass (52.7 ± 0.4 vs. 59.4 ± 1.0%, P < 0.001), strength (91.1 ± 1.3 vs. 124.9 ± 1.2 g, P < 0.0001), and locomotor activity (347.0 ± 14.4 vs. 432.7 ± 32.0 m, P < 0.001). Improvements in physical function were mediated in part by reductions in skeletal muscle inflammation (interleukin 6 and gp130, both P < 0.05), enhanced mitochondrial function, and improved endoplasmic reticulum homeostasis. Specifically, BAM15 activated mitochondrial quality control (PINK1‐ubiquitin binding and LC3II, P < 0.01), increased mitochondrial activity (citrate synthase and complex II activity, all P < 0.05), restricted endoplasmic reticulum (ER) misfolding (decreased oligomer A11 insoluble/soluble ratio, P < 0.0001) while limiting ER stress (decreased PERK signalling, P < 0.0001), apoptotic signalling (decreased cytochrome C release and Caspase‐3/9 activation, all P < 0.001), and muscle protein degradation (decreased 14‐kDa actin fragment insoluble/soluble ratio, P < 0.001).ConclusionsMitochondrial uncoupling by agents such as BAM15 may mitigate age‐related decline in muscle mass and function by molecular and cellular bioenergetic adaptations that confer protection against sarcopenic obesity.

Impact of high-intensity interval training with or without l-citrulline on physical performance, skeletal muscle, and adipose tissue in obese older adults.

BackgroundAging is associated with a progressive decline in skeletal muscle mass and strength as well as an increase in adiposity. These changes may have devastating impact on the quality of life of older adults. Mitochondrial dysfunctions have been implicated in aging‐related and obesity‐related deterioration of muscle function. Impairments in mitochondrial quality control processes (biogenesis, fusion, fission, and mitophagy) may underlie this accumulation of mitochondrial dysfunction. High‐intensity interval training (HIIT) was shown to improve muscle and mitochondrial function in healthy young and old adults and to improve body composition in obese older adults. Recent studies also positioned citrulline (CIT) supplementation as a promising intervention to counter obesity‐related and aging‐related muscle dysfunction. In the present study, our objectives were to assess whether HIIT, alone or with CIT, improves muscle function, functional capacities, adipose tissue gene expression, and mitochondrial quality control processes in obese older adults.MethodsEighty‐one‐old and obese participants underwent a 12 week HIIT with or without CIT on an elliptical trainer [HIIT‐CIT: 20 men/25 women, 67.2 ± 5.0 years; HIIT‐placebo (PLA): 18 men/18 women, 68.1 ± 4.1 years]. Handgrip and quadriceps strength, lower limb muscle power, body composition, waist circumference, and functional capacities were assessed pre and post intervention. Vastus lateralis muscle biopsies were performed in a subset of participants to quantify markers of mitochondrial content (TOM20 and OXPHOS subunits), biogenesis (TFAM), fusion (MFN1&2, OPA1), fission (DRP1), and mitophagy (Parkin). Subcutaneous abdominal adipose tissue biopsies were also performed to assess the expression of genes involved in lipid metabolism.ResultsHIIT‐PLA and HIIT‐CIT displayed improvements in functional capacities (P < 0.05), total (mean ± SD: HIIT‐PLA: +1.27 ± 3.19%, HIIT‐CIT: +1.05 ± 2.91%, P < 0.05) and leg lean mass (HIIT‐PLA: +1.62 ± 3.85%, HIIT‐CIT: +1.28 ± 4.82%, P < 0.05), waist circumference (HIIT‐PLA: −2.2 ± 2.9 cm, HIIT‐CIT: −2.6 ± 2.5 cm, P < 0.05), and muscle power (HIIT‐PLA: +15.81 ± 18.02%, HIIT‐CIT: +14.62 ± 20.02%, P < 0.05). Only HIIT‐CIT decreased fat mass (−1.04 ± 2.42%, P < 0.05) and increased handgrip and quadriceps strength (+4.28 ± 9.36% and +10.32 ± 14.38%, respectively, P < 0.05). Both groups increased markers of muscle mitochondrial content, mitochondrial fusion, and mitophagy (P < 0.05). Only HIIT‐CIT decreased the expression of the lipid droplet‐associated protein CIDEA (P < 0.001).ConclusionsHigh‐intensity interval training is effective in improving functional capacities, lean mass, muscle power, and waist circumference in obese older adults. HIIT also increases markers of mitochondrial biogenesis, mitochondrial fusion, and mitophagy. Importantly, adding CIT to HIIT results in a greater increase in muscle strength and a significant decrease in fat mass. The present study therefore positions HIIT combined with CIT as an effective intervention to improve the health status of obese older adults.

Relationship between eosinophils counts and muscle mass decline in older people with type 2 diabetes: A prospective study of the KAMOGAWA-DM cohort.

Sarcopenia has become an important issue in older individuals with type 2 diabetes. However, no previous studies investigated the relationship between eosinophil count and muscle mass decline. In this prospective cohort study, we aimed to investigate this relationship in older people with type 2 diabetes. Impedance body composition was used to assess body composition and skeletal muscle mass index (SMI, kg/m2) was calculated as appendicular muscle mass (kg)/height squared (m2). The decrease in SMI (kg/m2 per year) was calculated as (baseline SMI [kg/m2] - follow-up SMI [kg/m2]) divided by the follow-up period (years). The rate of SMI decrease (%) was calculated as follows: (decrease in SMI [kg/m2 per year] ÷ baseline SMI [kg/m2])×100; muscle mass decline was defined as the rate of SMI decrease of ≥0.5%. Complete blood counts, including eosinophil counts, were also measured. Among 141 participants, 54.6% experienced muscle mass decline during mean (standard deviation)19.4 (7.3) months of follow-up. The eosinophil counts of participants with muscle mass decline were higher than those of participants without muscle mass decline (216.5 [147.8] vs. 158.6 [113.1] cells/mm3, p=0.004). Eosinophil counts were negatively associated with the rate of SMI decrease according to Spearman's rank correlation coefficient (r=0.182, p=0.031). According to logistic regression analyses, there was the relationship between eosinophil counts and incident muscle mass decline after adjusting for covariates (odds ratio of Δ 1 incremental of logarithm (eosinophil counts) 2.04 (95% confidence interval 1.15-3.61, p=0.011). This study showed that eosinophil counts are associated with incident muscle mass decline. If an individual with type 2 diabetes has high eosinophil counts in blood tests, then it is necessary to pay more attention to the possibility of progression of muscle atrophy.

Nutritional status and quality of life are associated with risk of sarcopenia in nursing home residents: a cross-sectional study

Sarcopenia, which is characterized by an age-related decline in skeletal muscle mass, strength, and function, is an important geriatric syndrome that is closely related to the nutritional status and quality of life (QoL) of older adults. The aim of this study was to compare the nutritional status and QoL of nursing home residents according to sarcopenia. We hypothesized that a daily protein intake <1.2 g/kg is associated with a higher risk of sarcopenia. This study was performed with 172 older adults living a nursing home. Sarcopenia was defined according to the consensus of the European Working Group on Sarcopenia in Older People. The nutritional status was evaluated using the Mini Nutritional Assessment-Short Form, 24-hour dietary recall. Frailty was evaluated using the Fatigue, Resistance, Ambulation, Illnesses, and Loss of weight scale and health-related QoL was evaluated by the European Quality of Life-5 Dimensions scale. In addition to the anthropometric measurements associated with sarcopenia, QoL was also lower in sarcopenic individuals. The risk of malnutrition and frailty status were more prevalent among the sarcopenic individuals. In the multivariate logistic regression analysis, a higher QoL score was related with a low risk for sarcopenia, whereas the risk of malnutrition, a daily protein intake that was <1.2 g/kg/d, and being >80 years of age remained predictive of sarcopenia after adjustment. Sarcopenic nursing home residents have a great risk of malnutrition and lower QoL. This study showed that QoL, the risk of malnutrition, and daily protein intake are important factors as potential target areas for the management of sarcopenia in nursing home residents.

Higher uric acid serum levels are associated with sarcopenia in west China: a cross-sectional study

BackgroundSarcopenia is the decline in muscle strength and mass attributed to aging. The pathogenesis of sarcopenia may be triggered by oxidative stress and uric acid (UA) has strong antioxidant properties. The aim of this study was to investigate the relationship between UA and sarcopenia in community-dwelling adults of West China using the baseline data of West China Health and Aging Trend (WCHAT) study.DesignA cross-sectional study.Methods4236 adults aged 50 years or older in communities of west China were enrolled in this study. We applied Asian Working Group for Sarcopenia (AWGS) 2019 criteria to define sarcopenia. Muscle mass was measured using skeletal muscle index (SMI) based on bioimpedance analysis (BIA). Handgrip strength (HGS) and gait speed (GS) were recorded, respectively. Different variables like anthropometry measures, life styles, chronic disease and blood test were collected. General linear model was done to investigate the relationship between UA and HGS/GS/SMI, adjusting age, ethnic groups, sleeping quality, education level, cognitive function, smoking history, drinking history, ADL score, and chronic disease.ResultsParticipants were grouped according to UA quartiles by gender. After adjusting for potential confounders, a negative association between serum UA levels and sarcopenia was shown both in men and women. And a significant association between serum UA levels and HGS in women was shown as an inverted J shape. Besides, a positive association between the UA quartiles and SMI was observed, irrespective of gender.ConclusionsOur results showed that higher uric acid levels were significantly correlated with higher muscle mass and grip strength among Chinese adults aged over 50. Higher UA serum levels might slow down the progression of sarcopenia.

Muscle mitochondrial energetics predicts mobility decline in well-functioning older adults: The baltimore longitudinal study of aging.

BackgroundMuscle mitochondrial dysfunction is associated with poor mobility in aging. Whether mitochondrial dysfunction predicts subsequent mobility decline is unknown.MethodsWe examined 380 cognitively normal participants aged 60 and older (53%women, 22%Black) who were well‐functioning (gait speed ≥ 1.0 m/s) and free of Parkinson's disease and stroke at baseline and had data on baseline skeletal muscle oxidative capacity and one or more mobility assessments during an average 2.5 years. Muscle oxidative capacity was measured by phosphorus magnetic resonance spectroscopy as the post‐exercise recovery rate of phosphocreatine (kPCr). Mobility was measured by four walking tests. Associations of baseline kPCr with mobility changes were examined using linear mixed‐effects models, adjusted for covariates. In a subset, we examined whether changes in muscle strength and mass affected these associations by adjusting for longitudinal muscle strength, lean mass, and fat mass.ResultsLower baseline kPCr was associated with greater decline in all four mobility measures (β, p‐value: (0.036, 0.020) 6‐m usual gait speed; (0.029, 0.038) 2.5‐min usual gait speed; (0.034, 0.011) 6‐m rapid gait speed; (−0.042, <0.001) 400‐m time). In the subset, further adjustment for longitudinal muscle strength, lean mass, and fat mass attenuated longitudinal associations with changes in mobility (Δβ reduced 26–63%).ConclusionAmong initially well‐functioning older adults, worse muscle mitochondrial function predicts mobility decline, and part of this longitudinal association is explained by decline in muscle strength and mass. Our findings suggest that worse mitochondrial function contributes to mobility decline with aging. These findings need to be verified in studies correlating longitudinal changes in mitochondrial function, muscle, and mobility performance.

Physical Activity Related to Body Muscle Mass Index and Stiffness Index in 7-to-10-Year-Old Girls.

The relationship between moderate-to-vigorous physical activity (MVPA) performance time and body muscle mass and stiffness index in pre-puberty school-aged girls has not been fully elucidated. The effect of sexual maturity on bone mass is more pronounced in girls. This study aimed to clarify the relationship between MVPA performance time and the above-mentioned factors. This was a prospective, population-based cohort study of 111 girls aged 7–10 years. Data were collected via medical examination, clinical measurements, and questionnaires. Spearman’s ρ analysis was used to determine the association between skeletal muscle mass index (SMI) and stiffness index, muscle strength, and MVPA performance time. Participants who met the recommended MVPA level accounted for only 24.3% (n = 27) of all participating girls (n = 111). The following factors were significantly positively correlated with MVPA level at spearman’s ρ analysis: SMI (r = 0.303, p = 0.001), stiffness index (r = 0.229, p = 0.015), grip strength (r = 0.283, p = 0.003), back muscle strength (r = 0.197, p = 0.038), and standing long jump distance (r = 0.288, p = 0.002). Multiple regression analysis’s results revealed that SMI (β = 0.237; p = 0.024) was associated with MVPA performance time. These results can help school-aged girls to pay adequate attention to having healthy physical activity habits to prevent the decline of skeletal muscle mass, stiffness index, and body muscle strength.

Cardiac troponin T and autoimmunity in skeletal muscle aging.

Age-related muscle mass and strength decline (sarcopenia) impairs the performance of daily living activities and can lead to mobility disability/limitation in older adults. Biological pathways in muscle that lead to mobility problems have not been fully elucidated. Immunoglobulin G (IgG) infiltration in muscle is a known marker of increased fiber membrane permeability and damage vulnerability, but whether this translates to impaired function is unknown. Here, we report that IgG1 and IgG4 are abundantly present in the skeletal muscle (vastus lateralis) of ~ 50% (11 out of 23) of older adults (&gt; 65years) examined. Skeletal muscle IgG1 was inversely correlated with physical performance (400m walk time: r = 0.74, p = 0.005; SPPB score: r = - 0.73, p = 0.006) and muscle strength (r = - 0.6, p = 0.05). In a murine model, IgG was found to be higher in both muscle and blood of older, versus younger, C57BL/6 mice. Older mice with a higher level of muscle IgG had lower motor activity. IgG in mouse muscle co-localized with cardiac troponin T (cTnT) and markers of complement activation and apoptosis/necroptosis. Skeletal muscle-inducible cTnT knockin mice also showed elevated IgG in muscle and an accelerated muscle degeneration and motor activity decline with age. Most importantly, anti-cTnT autoantibodies were detected in the blood of cTnT knockin mice, old mice, and older humans. Our findings suggest a novel cTnT-mediated autoimmune response may be an indicator of sarcopenia.

Primary skeletal muscle cells from chronic kidney disease patients retain hallmarks of cachexia in vitro.

BackgroundSkeletal muscle wasting and dysfunction are common characteristics noted in people who suffer from chronic kidney disease (CKD). The mechanisms by which this occurs are complex, and although progress has been made, the key underpinning mechanisms are not yet fully elucidated. With work to date primarily conducted in nephrectomy‐based animal models, translational capacity to our patient population has been challenging. This could be overcome if rationale developing work could be conducted in human based models with greater translational capacity. This could be achieved using cells derived from patient biopsies, if they retain phenotypic traits noted in vivo.MethodsHere, we performed a systematic characterization of CKD derived muscle cells (CKD; n = 10; age: 54.40 ± 15.53 years; eGFR: 22.25 ± 13.22 ml/min/1.73 m2) in comparison with matched controls (CON; n = 10; age: 58.66 ± 14.74 years; eGFR: 85.81 ± 8.09 ml/min/1.73 m2 ). Harvested human derived muscle cells (HDMCs) were taken through proliferative and differentiation phases and investigated in the context of myogenic progression, inflammation, protein synthesis, and protein breakdown. Follow up investigations exposed HDMC myotubes from each donor type to 0, 0.4, and 100 nM of IGF‐1 in order to investigate any differences in anabolic resistance.ResultsHarvested human derived muscle cells isolated from CKD patients displayed higher rates of protein degradation (P = 0.044) alongside elevated expression of both TRIM63 (2.28‐fold higher, P = 0.054) and fbox32 (6.4‐fold higher, P < 0.001) in comparison with CONs. No differences were noted in rates of protein synthesis under basal conditions (P > 0.05); however, CKD derived cells displayed a significant degree of anabolic resistance in response to IGF‐1 stimulation (both doses) in comparison with matched CONs (0.4 nm: P < 0.001; 100 nM: P < 0.001).ConclusionsIn summary, we report for the first time that HDMCs isolated from people suffering from CKD display key hallmarks of the well documented in vivo phenotype. Not only do these findings provide further mechanistic insight into CKD specific cachexia, but they also demonstrate this is a reliable and suitable model in which to perform targeted experiments to begin to develop novel therapeutic strategies targeting the CKD associated decline in skeletal muscle mass and function.