Reduced Muscle Mass Research Articles

Deletion of Myostatin Significantly and Preferentially Improves Muscle Function in a Sex-Dependent Manner in Both an Obese and Aging Mouse Model

Skeletal muscle mass and function are essential components of health and homeostasis. In addition to its role in balance and locomotion, skeletal muscle is the body’s largest metabolic reservoir, absorbing significant amounts of glucose and amino acids from the blood stream. The loss of muscle mass is associated with impaired glucose tolerance, threatens vascular health and contributes to cardiovascular disease in obese and aging (sarcopenic) populations, along with driving overall mortality. The myokine myostatin (GDF-8) is a potent negative regulator of skeletal muscle growth that is upregulated in humans and animal models of obesity and aging. Loss of myostatin is known to increase the number of glycolytic muscle fibers and has been shown to correct indices that govern cardiometabolic health in obesity and aging, improving endothelial function and glucose homeostasis, and protecting against renal injury and hypertension. However, these studies have largely been conducted using male mice, leaving the question regarding the effectiveness of myostatin deletion on skeletal muscle function, independent of sex, largely unexplored. As such, our hypothesis is that the deletion of myostatin will improve skeletal muscle function in both male and female mice, regardless of the disease phenotype being obesity or aging. Young (3-5 mo.) lean and obese mice were used, along with aged (18-24 mo.) mice. The obese db/db model was utilized as it is a well characterized model of hyperphagia that results in obesity and subsequent metabolic disease, including significant whole-body adiposity and reduced muscle mass. On this background we have crossed mice harboring constitutive genetic deletion of myostatin to reverse muscle loss. Thus, myostatin deletion was crossed onto the relevant backgrounds in combination with aging or obesity and included both sexes. Muscle function was assessed in all groups using in vivo plantarflexion. Young male mice demonstrated an ~20% increase in force production compared to the females. Results show that aging and obesity inhibited skeletal muscle function in both sexes, with female mice showing a lessened impact of obesity or aging. Myostatin deletion improved muscle function in male mice, returning both obesity-derived weakness and aging-induced sarcopenia back to levels of young control. However, female mice without myostatin experienced a relative gain-of-function, with force production significantly exceeding that of the young control. The implication of these results is that weight loss may be more effective in protecting muscle function in diseases in the male population whereas myostatin inhibition, either pharmaceutically or with prescription exercise, may result in greater improvements in the female sex comparatively. This research gratefully acknowledges support from the NIA (K01 AG064121), OCAST (HR21-045-1) and the Niblack Research Scholars Program. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The use of urinary kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin for diagnosis of hepato-renal syndrome in advanced cirrhotic patients

Background Chronic liver disease is a common and important clinical problem.Hepatorenal syndrome (HRS) is a life threatening complication. Serum creatinine (Cr) remains the only conventional indicator of renal function. However, the interpretation of serum Cr level can be confounded by malnutrition and reduced muscle mass often observed in patients with severe liver disease. Here, we present a cross-sectional study to explore the sensitivity and specificity of other markers as urinary KIM-1 and NGAL for cases of HRS. Methods Cross-sectional study was conducted on 88 patients who were admitted to Alexandria main university hospital. Enrolled patients were divided in two groups; group 1: patients with advanced liver cirrhosis (child B and C) who have normal kidney functions while group 2: patients who developed HRS. Stata© version 14.2 software package was used for analysis. Results Group 1 included 18 males and 26 females compared to 25 males and 19 females in group 2 (p = 0.135). Only the urinary KIM-1 showed a statistically significant difference between both groups in the multivariate logistic regression analysis adjusted for gender, serum bilirubin, serum albumin, INR, serum K, AST and ALT levels. Conclusion In conclusion, our study aligns with prior research, as seen in the consistent findings regarding Urinary NGAL elevation in cirrhotic patients with AKI. Urinary KIM-1, independent of Urinary NGAL, may have a role in precisely distinguishing between advanced liver cirrhosis and HRS and merits further exploration.

Impact of Hindlimb Disuse on Sepsis-Induced Myopathy in Older Adult Mice

BACKGROUND: Sepsis, a life-threatening condition due to an overactive immune response, adversely affects multiple organ systems. Despite its significance of accounting for 40% of total body mass, the skeletal muscle system is considered the forgotten organ system affected by sepsis. In addition to the inflammatory aspects of sepsis, patients in the intensive care unit (ICU) frequently experience prolonged periods of bed rest, which can lead to muscle disuse-induced myopathy characterized by muscle atrophy, weakness, and impaired regenerative capacity. Despite the higher incidence of sepsis in bedridden older adults, most research on sepsis-induced myopathy primarily focuses on younger adults under conditions that do not mimic bed rest. In this study, we simulated the clinical conditions of older adult ICU patients by combining sepsis with hindlimb disuse. Our hypotheses were that the combination of sepsis, disuse, and aging would exacerbate muscle atrophy and weakness, while also reducing the number of regenerative stem cells in muscle tissue. Methods: To investigate the functional and morphological responses of skeletal muscle to sepsis, we conducted experiments on 78-week-old male wild-type C57Bl6 mice. They underwent either cecal ligation and puncture (CLP, n = 17) or Sham (n = 14) surgeries. Four days post-surgery, the animals were allocated to hindlimb suspension (HLS — CLP, n=9; Sham, n=10) or normal ambulation (NA — CLP, n=8; Sham, n=4) for seven days. Terminal experiments were conducted after hindlimb suspension or normal ambulation treatments. We assessed peak force production ex vivo in solei muscles, examined the cross-sectional area (CSA) of relevant hindlimb muscles using immunohistochemistry, and quantified the abundance of stem cells through immunohistochemistry (e.g., PAX7+ cells) in muscle sections. Additionally, we evaluated markers of senescence by measuring the protein abundance of p16 and p53 in hindlimb muscle homogenates. Results: CLP surgery resulted in 50% mortality rate (p<0.05). Percentage body mass loss was as follows: 5.3 ± 4.2 for Sham/NA group, 13.3 ± 5.2 for Sham/HLS group, 7.3 ± 4.4 for CLP/NA group, and 17.7 ± 5.5 for CLP/HLS group. Peak absolute force was significantly lower in Sham/HLS and CLP/HLS compared to Sham/NA (Sham/NA = 277±2.4, Sham/HLS = 189±28.4, CLP/NA = 264±23.0, CLP/HLS = 180±48.9 mN, p<0.05). Mice exposed to CLP/HLS displayed a higher cumulative fiber area at smaller fiber sizes (800 to 1000 μm2) (p<0.05), indicating muscle atrophy. CLP/NA caused a 9.8% reduction in solei muscle mass (p < 0.05), while CLP/HLS led to an additional 30% loss in solei mass (p<0.05). Furthermore, CLP/HLS significantly decreased the number of PAX7+ stem cells by 75% (p<0.05). Notably, p16 was significantly increased in response to CLP/HLS (p<0.05), while no changes were observed in p53 abundance. CONCLUSION: This study demonstrates the role of muscle disuse in exacerbating skeletal muscle functional and morphological abnormalities in older adult septic mice, emphasizing the critical contribution of disuse to the pathophysiology of sepsis-induced myopathy. NIH R21AG072011 to OL. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A novel preclinical model of human lung cancer cachexia

Most patients with lung cancer are afflicted with cancer cachexia (CC), a syndrome characterized by wasting of muscle and fat tissues, which leads to poor treatment response and increased mortality. Pre-clinical models used to study CC often do not mimic the human condition, which may explain why there are no approved treatments for CC. To overcome this barrier, we sought to develop a model of lung CC that better recapitulates the pathoetiological characteristics of human lung CC using mice with a tamoxifen-inducible, lung epithelial cell (club cell)-specific KrasG12D allele ( G12D mice). We hypothesized that this model would mimic human CC in tumor location and burden, rate of progression, and tumor-driven tissue wasting. Following induction by tamoxifen injection, adenocarcinomas developed in the terminal bronchioles as early as 3.5 weeks post-induction and were accompanied by loss of 15% of animal body weight over a 12-week period. This weight loss began at 6 weeks and yielded a slow rate of CC progression (-1.9%/week) relative to currently available lung CC models (-5-10%/week). Body weight loss resulted from reductions in hindlimb muscle mass (18-30%) and profound depletion of inguinal and gonadal adipose tissue depots (60-70%) compared to age-matched wild-type (WT) littermates. At 6 weeks post-induction, fat tissue was reduced at the tissue and cellular levels while reductions in hindlimb muscle weight and fiber size were not observed. This fat loss corresponded with increased serum glycerol levels at 6 and 12 weeks, a metabolic characteristic that was also found in patients with lung cancer receiving treatment. Lung organoids were developed from G12D and WT mice. G12D organoids exhibited similarities in gene expression to human lung tumors ( RNAseq) and their conditioned medium (CM) elicited glycerol release from cultured 3T3L1 adipocytes compared to CM from WT organoids, suggesting that tumor-derived factors may contribute to early adipose tissue atrophy. Collectively, these findings suggest that G12D mice may be a valuable model, well-suited to identify mechanisms leading to CC and test preventative therapies. NIH R01 AR065826(MJT), NCI R21 CA283492(MJT), T32- HL076122-18(DBS/MEP), R01 CA273238 (YJ-H) and the University of Vermont Cancer Center. Funding support for RNAseq provided by Zymo Impact Initiative Grant (DBS). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects of Aging and Fatigue on Human Skeletal Muscle Cellular Contractile Function

Aging is associated with a reduction in skeletal muscle mass and function, known as sarcopenia. While reductions in contractile force are typically explained by loss in muscle cellular cross sectional area (CSA) loss of contractile power during high velocity contractions exceed reductions in force and cannot be solely explained by loss of muscle size and are observed at the single fiber within the same myosin heavy chain isoform (MHC). These phenomenon may be explained by myosin binding protein C (MyBP-C), which is known to modulate contractile force and velocity in a phosphorylation-dependent manner in both cardiac and skeletal muscle. Few studies have investigated the inherent contractile performance of single fibers between old and young adults, and none have explored the effects of altered MyBP-C phosphorylation on single fiber function. Therefore, the PURPOSE of this study was to investigate the effects of age and fatigue-induced MyBP-C phosphorylation on single fiber contractile performance. We HYPOTHESIZED that isometric tension will be enhanced in older adults but velocity and power will be reduced, and fatigue will enhance velocity and power in single fibers. To test this hypothesis, we recruited 4 young (18-35) and 3 older (65-80) adult males to perform a single bout of unilateral knee extensions at 30% maximal voluntary isometric contraction (MVIC) until task failure. Immediately following, a bilateral biopsy of the vastus lateralis (VL) muscle was performed on the fatigued and non-fatigued control limbs. Tissue was either flash frozen for western blot or prepared for mechanical analysis of single fiber tension (Tmax), velocity (Vmax), and power (Pmax) under optimal intracellular metabolic conditions. Our analyses were limited to MHC IIA due to differences in fiber type distribution between the groups. Our RESULTS showed that neither age nor fatigue had an effect on contractile performance in MHC IIA fibers. However, independent analysis of fatigue within age groups suggest trends towards an increase in velocity (p=0.055) in young (MHC IIA) and reduction in tension (p=0.085) in old (MHC I) adult fibers. We CONCLUDE that fatigue may modulate contractile function in the single fiber in an age- and fiber-type dependent manner. Future studies will be aimed at collecting multiple fiber types and investigating the role of biological sex. Wu Tsai Human Performance Alliance. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Augmented muscle mass blunts aging-induced cerebrovascular oxidant stress and inflammation

Cerebrovascular dysfunction is a key driver in the cognitive and sensorimotor decline that accompanies aging, contributing to the overall progression of vascular dementia. Exercise is an effective intervention to improve brain health and cognitive function, demonstrating positive effects on cerebral vasculature via a reduction in oxidant stress, thus delaying or partially reversing dementia symptoms. Age-related muscle loss (sarcopenia), however, is prevalent in adults over 50 and sarcopenic older individuals are frequently unable to take advantage of regular exercise, the most effective therapy to reduce risk of cognitive impairment, at a level that confers benefit. Interventions that can effectively replicate the effect of exercise are thus urgently needed to address the medical needs of a large population at exceedingly elevated risk for age-related cognitive impairment. The objective of the work is to determine if augmented muscle mass, a by-product of exercise, can ameliorate both skeletal and cerebrovascular dysfunction in an aging mouse model. Myokine myostatin is a potent negative regulator of skeletal muscle growth that contributes to reduced muscle mass in many muscle-wasting diseases, including aging. To date, research has focused on the protective effect of augmented muscle mass, using genetic or pharmaceutical inhibition of myostatin, in young and obese animals. Our hypothesis is that augmented muscle mass, via myostatin deletion, will improve muscle function and further, blunt the increase in oxidant stress and inflammation that drive cerebrovascular dysfunction in the aging brain. Young adult (3 mo.) and aged (24 mo.) male C57Bl/6J mice were used as controls, in combination with aged mice (24 mo.) with myostatin constitutively deleted. Augmented muscle mass and function were assessed using in vivo plantarflexion. Oxidant stress and inflammatory makers were assessed in micro vessels isolated from the whole brain, using commercially available ELISA’s and mRNA expression. Vascular function is being assessed using pressure myography and immunohistochemistry using the middle cerebral artery. Results show that augmented muscle mass, via myostatin deletion, was successful at increasing muscle mass in the aging mouse, blunting sarcopenia, and improving skeletal muscle function. Further, the aging cerebrovasculature had significantly increased expression of two of the NADPH oxidase isoforms (NOX1, NOX4), along with pivotal cytokines/chemokines associated with vascular inflammation, activation of microglia and astrocytes, and neuroinflammation (IL-1β and CCL5/RANTES). Biomarkers of oxidant stress (3-nitrotyrosine and 8-isoprostane) were also significantly elevated with aging. Taken together, augmented muscle mass may be an effective therapeutic target to prevent and rescue cerebrovascular function and inhibit cognitive decline in an aging population. This research gratefully acknowledges support from the NIA (K01 AG064121), OCAST (HR21-045-1) and the Niblack Research Scholars Program. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Concerted regulation of skeletal muscle metabolism and contractile properties by the orphan nuclear receptor Nr2f6.

The maintenance of skeletal muscle plasticity upon changes in the environment, nutrient supply, and exercise depends on regulatory mechanisms that couple structural and metabolic adaptations. The mechanisms that interconnect both processes at the transcriptional level remain underexplored. Nr2f6, a nuclear receptor, regulates metabolism and cell differentiation in peripheral tissues. However, its role in the skeletal muscle is still elusive. Here, we aimed to investigate the effects of Nr2f6 modulation on muscle biology in vivo and in vitro. Global RNA-seq was performed in Nr2f6 knockdown C2C12 myocytes (N=4-5). Molecular and metabolic assays and proliferation experiments were performed using stable Nr2f6 knockdown and Nr2f6 overexpression C2C12 cell lines (N=3-6). Nr2f6 content was evaluated in lipid overload models in vitro and in vivo (N=3-6). In vivo experiments included Nr2f6 overexpression in mouse tibialis anterior muscle, followed by gene array transcriptomics and molecular assays (N=4), ex vivo contractility experiments (N=5), and histological analysis (N=7). The conservation of Nr2f6 depletion effects was confirmed in primary skeletal muscle cells of humans and mice. Nr2f6 knockdown upregulated genes associated with muscle differentiation, metabolism, and contraction, while cell cycle-related genes were downregulated. In human skeletal muscle cells, Nr2f6 knockdown significantly increased the expression of myosin heavy chain genes (two-fold to three-fold) and siRNA-mediated depletion of Nr2f6 increased maximal C2C12 myocyte's lipid oxidative capacity by 75% and protected against lipid-induced cell death. Nr2f6 content decreased by 40% in lipid-overloaded myotubes and by 50% in the skeletal muscle of mice fed a high-fat diet. Nr2f6 overexpression in mice resulted in an atrophic and hypoplastic state, characterized by a significant reduction in muscle mass (15%) and myofibre content (18%), followed by an impairment (50%) in force production. These functional phenotypes were accompanied by the establishment of an inflammation-like molecular signature and a decrease in the expression of genes involved in muscle contractility and oxidative metabolism, which was associated with the repression of the uncoupling protein 3 (20%) and PGC-1α (30%) promoters activity following Nr2f6 overexpression in vitro. Additionally, Nr2f6 regulated core components of the cell division machinery, effectively decoupling muscle cell proliferation from differentiation. Our findings reveal a novel role for Nr2f6 as a molecular transducer that plays a crucial role in maintaining the balance between skeletal muscle contractile function and oxidative capacity. These results have significant implications for the development of potential therapeutic strategies for metabolic diseases and myopathies.

Sarcopenia em pessoas idosas: concordância entre métodos preditores

Sarcopenia is a relevant clinical condition worldwide. Its prevalence ranges from 5% to 13% in the elderly aged 65 years and over. Over 80 years, this value can reach 50%, demonstrating the influence of age on the development of the disease. Its diagnosis is based on reduced muscle mass, associated with decreased strength and/or low muscle function. The gold standard for diagnosing the disease is Dual-energy X-ray absorptiometry, but it is inaccessible due to its high cost and diagnostic complexity. Thus, alternative methods for screening for sarcopenia, such as: sit and stand test (TSL), calf circumference (CP) and manual strength test (FPM), SARC-F questionnaire are applied. Defining methods suitable for the outpatient setting is essential for both screening and diagnosis of the disease. The present study aimed to analyze whether there is agreement between predictive methods used to estimate the existence of sarcopenia in the elderly. This is a cross-sectional study carried out with 27 healthy elderly people (23 women and 4 men). The predictive methods were measuring CP, FPM, TSL and Ishii Probability Score (ISHII). The agreement between the classifications was used the Kappa statistic. All predictive methods identified sarcopenic and non-sarcopenic individuals. There was no agreement in the combinations: CTS x FPM; TSL x FPM and; TSL x ISHII. As for the association between the CTS and TSL methods, there was a moderate agreement between the predicted values (k=0.43; p=0.006). Conclusion: Different predictive methods promote different sarcopenia diagnoses. A moderate agreement was observed for the combination between CTS and TSL predictors. It should be noted that the association between different tests is an option to be evaluated.

The relationship between muscle strength and quality with functional performance in women mid- to long-term after Roux-en-Y gastric bypass

BACKGROUND: The reduction of muscle mass and strength commonly observed after bariatric surgery might negatively affect the individual physical function. Muscle quality is also of functional relevance in different populations, but its significance in patients who underwent bariatric surgery has yet to be explored. OBJECTIVE: To examine the association between muscle strength and quality with physical function in women mid- to long-term after Roux-en-Y gastroplasty (RYGB). METHODS: In this cross-sectional study, 133 women (43.7± 9.9 years) who have undergone RYGB at least two years before the study were included. All participants underwent body composition evaluation using DEXA and knee extensors peak moment (PM) using an isokinetic dynamometer. Muscle quality (MQ) was obtained through the ratio between absolute PM and dominant leg fat-free mass. Physical function was measured through the 30-second sit-to-stand (30-STS), 6-minute walking (6-MWT), and timed up-and-go (TUG) tests. RESULTS: Differences between PM tertiles were observed for 30-STS and 6-MWT tests. However, statistical significance disappeared when adjusting for age. Regarding PM relative to body weight, all functional tests were significantly different between tertiles. Comparing functional performance according to MQ tertiles, differences were found for 30-STS and 6-MWT tests, but significance disappeared when adjusting for age. Absolute PM was correlated to the 30-STS performance and 6-MWT, while PM relative to body mass and MQ were correlated with all functional tests. CONCLUSIONS: Muscle strength and quality seem to be associated with physical function in women mid-to-long-term after RYGB, but strength relative to bodyweight outperformed absolute strength and MQ.

Clinical Impact of Malnutrition According to the Global Leadership Initiative on Malnutrition Criteria Combined With Kidney Dysfunction to Determine Mortality in Inpatients

ObjectiveThe clinical impact of malnutrition based on the Global Leadership Initiative on Malnutrition (GLIM) criteria in patients with kidney dysfunction remains poorly understood. This study investigated the usefulness of GLIM criteria for malnutrition predicting mortality in patients with kidney dysfunction and different clinical renal states, including no kidney disease (NKD), acute kidney injury (AKI), and chronic kidney disease (CKD). MethodsThis single-center retrospective cohort study included 6,712 patients aged ≥18 admitted between 2018 and 2019. The relationship between the estimated glomerular filtration rate (eGFR) groups, nutritional status based on the GLIM criteria, and incidence of all-cause mortality was evaluated using multivariate Cox proportional hazards (CPH) models. Malnutrition was defined as at least one phenotype (weight loss, low body mass index (BMI), or reduced muscle mass) and one etiological criterion (reduced intake/assimilation or disease burden/inflammation). ResultsMultivariate CPH models showed that eGFR ≤29 (vs. eGFR: 60–89, adjusted HR = 1.84, 95% CI: 1.52–2.22), 30–59 (vs. eGFR: 60–89, adjusted HR = 1.40, 95% CI: 1.20–1.64), and ≥90 (vs. eGFR: 60–89, adjusted HR = 1.40, 95% CI: 1.14–1.71), moderate and severe malnutrition (vs. without malnutrition, adjusted HR = 1.38 [1.18–1.62] and 2.18 [1.86–2.54], respectively) were independently associated with the incidence of death. The all-cause mortality rate was higher in patients with malnutrition or eGFR ≤29 (adjusted HR, 3.31; 95% CI: 2.51–4.35) than in patients without malnutrition or eGFR 60–89. Furthermore, moderate and severe malnutrition (vs. no malnutrition) was independently associated with death in patients with NKD, AKI, and CKD. ConclusionMalnutrition based on the GLIM criteria was associated with increased all-cause mortality in inpatients, and malnutrition combined with kidney dysfunction was associated with a higher risk of mortality. Furthermore, patients with NKD, AKI, and CKD showed an association between malnutrition based on GLIM criteria and mortality.

Impact of detraining on the health of individuals with spinal cord injury: a systematic review

Introduction: Spinal cord injury (SCI) is a debilitating condition that causes motor, physiological, and sensory impairments, potentially leading to permanent disability, increased morbidity, and mortality, ultimately impacting an individual's quality of life (QoL). Physical exercise emerges as an effective alternative to mitigate these consequences and uphold the autonomy and QoL for this population. Detraining (DT), defined as the partial or total loss of adaptations induced by physical training in response to its complete interruption or insufficient stimulus, represents a significant concern. The objective of this systematic review was to conduct a comprehensive literature review regarding the current state of knowledge on the potential impacts of DT on the health of individuals with SCI. Method: The search was conducted on PubMed, Web of Science, Embase, SPORTDiscus, and Cochrane databases using relevant English terms (("Detraining") AND ("Spinal Cord Injury")) and their synonyms. Due to the limited number of studies addressing this topic, no specific time frame was set for study eligibility. Results: The literature search was performed in November 2023, yielding 42 results, from which 15 remained after removing duplicates. Two articles were excluded following title analysis. Thirteen abstracts were reviewed, and 7 were excluded, leaving 6 articles for full analysis. Due to the nature of the studies, a meta-analysis was not conducted. Conclusion: DT resulted in alterations in body composition (BC), including increased body fat and reduced muscle mass, especially following the interruption of testosterone-associated training. Additionally, the cessation of training impacted the metabolic profile, leading to changes in glucose, lipids, and insulin sensitivity. Furthermore, hemodynamic variables, such as blood pressure (BP) and heart rate (HR), underwent changes, elevating the risk of cardiovascular complications. Regarding cardiorespiratory components, there was a decline in peak oxygen consumption (VO2peak) following the DT period. Halting exercise can lead to detrimental health consequences, underscoring the imperative of maintaining consistent physical training for these individuals.

Prevalence of Malnutrition in a Group of Institutionalized Psychogeriatric Patients Using Different Diagnostic Criteria.

Malnutrition (MN) is a highly prevalent condition in the elderly. It is associated with functional impairment, disability, frailty, and sarcopenia. The aim was to analyze the capacity of GLIM and ESPEN criteria to diagnose MN in a sample of institutionalized psychogeriatric patients. Clinical and anthropometric data were collected in a cross-sectional study. Patients' frailty, dependence, functional capacity, MNA, hand-grip strength (HS), and sarcopenia were evaluated. Body composition (BC) was estimated by conventional bioimpedance analysis. MN diagnosis was established using the ESPEN and the GLIM criteria based on fat-free mass index (GLIM-FFMI), appendicular skeletal muscle mass index (GLIM-ASMMI), skeletal muscle mass index (GLIM-SMMI), and HS (mGLIM). Ninety-two patients (57.6% men; mean age: 79.4 years) were studied. Depending on the diagnosis criteria, MN prevalence was between 25% (ESPEN) and 41.3% (GLIM-SMMI). Agreement between ESPEN and all GLIM criteria was poor, but it was excellent between all GLIM criteria (kappa > 0.8). Phenotypic criteria carried more weight in the diagnosis of MN than etiological ones. Depending on the parameter used, the prevalence of reduced muscle mass was notably different. Differences in BMI, BC, inflammation, and albumin are detected by the GLIM-FFMI criteria in the MN and non-MN subjects. Also, this criterion is the only one that identified differences in phase angle (PhA) between these groups. In the elderly, PhA can be very useful to monitor nutritional status.

Mobility and strength training with and without protein supplements for pre-frail or frail older adults with low protein intake: the Maximising Mobility and Strength Training (MMoST) feasibility randomised controlled trial protocol.

Background Frailty is a common syndrome affecting older people and puts them at risk of hospitalisation, needing care or death. First signs of frailty include reduced muscle strength and mobility decline. A key cause of mobility decline as we age is sarcopenia (age related reduction in muscle strength and mass). Poor nutrition contributes to sarcopenia. A shortfall in protein is associated with reduced muscle mass and strength. This may be due to inadequate intake but also because older people have higher protein needs, especially those with multimorbidity. We need to develop effective treatment to reduce or slow the onset of frailty and mobility decline. Exercise is a recommended treatment. Protein supplements to address the shortfall in protein have the potential to enhance the benefit of regular exercise in frail or pre-frail older adults. This has yet to be definitively demonstrated. Aim To establish the feasibility of conducting an RCT evaluating mobility and strength training with or without protein supplements for people over 60 years old who are frail or pre-frail with a low protein intake. Methods A multicentre, parallel, 2-group, feasibility RCT. Participants (recruitment target = 50) with problems walking, low protein intake and classified as frail or pre-frail will be recruited from four NHS Physiotherapy community services. Participants will be randomised (secure computer-generated: 1:1) to receive 24 weeks of mobility and strength training (delivered in 16 group sessions plus home exercises) or 24 weeks of mobility and strength training with daily protein supplements. Primary feasibility objectives are to estimate 1) ability to screen and recruit eligible participants, 2) intervention fidelity, adherence, and tolerance and 3) retention of participants at follow up. Secondary objectives are to 1) test data collection procedures, 2) assess data completeness and 3) confirm sample size calculation for a definitive RCT. Registration ISRCTN Registry (ISRCTN30405954; 18/10/2022).

Reduced Muscle Mass and Muscle Quality in Patients with Intermittent Claudication due to Peripheral Artery Disease

ObjectivePeripheral arterial disease (PAD) is associated with reduced muscle mass and quality, but the effects of leg ischemia caused by PAD on muscle quality remain poorly understood. The purpose of this study was to evaluate leg muscle mass and muscle quality in patients with intermittent claudication due to PAD using bioelectrical impedance analysis (BIA). MethodsOne hundred forty-one patients with intermittent claudication due to PAD who visited Tokyo Medical University Hospital from April 2019 to April 2020 were retrospectively analyzed. Leg ischemia was assessed using ankle-brachial index (ABI). The skeletal muscle mass (SMM) assessed leg muscle mass, while the phase angle (PhA) assessed leg muscle quality using BIA. ResultsA total of 282 legs in 141 patients were included in the analysis. Leg PhA and SMM showed a decreasing trend according to the severity of leg ischemia (borderline/no ischemia: 2.80 ± 0.50 kg/m2, 4.38 ± 0.94°; mild ischemia: 2.83 ± 0.49 kg/m2, 4.33 ± 1.03°; moderate/severe ischemia: 2.50 ± 0.40 kg/m2, 3.89 ± 0. 88°; p<0.001 and p=0.020, respectively). The ABI was moderately correlated with leg SMM (B=0.347, β=0.134, p<0.001) and leg PhA (B=0.577, β=0.111, p=0.013) after adjustment for all significant covariates. Leg PhA was moderately correlated with leg SMM (r = 0.318, p < 0.001). ConclusionsLeg ischemia, especially when moderate or severe, has an adverse effect on both muscle mass and quality in the lower extremities and is associated with skeletal muscle myopathy.

The multidirectional assessment of moderate caloric restriction and metformin treatment in obese patients.

Obesity treatment is often burdensome for patients. We used the combination of moderate caloric restriction (CR) with hypoglycemic metformin to assess their multidirectional effect in obese patients. One group was treated only with moderate CR (n=21) the second was treated with moderate CR and 800 mg metformin twice daily (n=23). Serum was drawn before and after treatment. The following parameters were monitored: anthropometric, cardiovascular, inflammatory, metabolic, and markers characteristic for thyroid, liver, pancreas, and kidney functions. Both tested groups did not significantly differ in most tested parameters after the treatment. Two groups reduced anthropometric parameters (body mass, body mass index (BMI), waist circumference) and fat mass but also muscle and fat-free mass, improving systolic blood pressure, insulin and leptin concentration, insulin sensitivity, leptin to adiponectin ratio, and inflammatory markers. Unfortunately, there was little impact on improving dyslipidemia and the thyroid and liver parameters. Free triiodothyronine (fT3) and gamma glutamyl transferase (GGT) activity were decreased in both groups, but triglycerides were reduced only in patients treated with moderate CR. Metformin with CR treatment decreases uric acid and aspartate aminotransferase (AspAT) activity. Metformin treatment with moderate CR in obese patients mainly improved insulin sensitivity, resulting in a reduction of patients with glucose intolerance, improved anthropometric, cardiovascular, and inflammatory mediators, and only slightly enhanced liver and thyroid function. No changes in kidney and pancreas function were observed during the treatment. In conclusion, eight weeks of CR alone and CR with metformin in obese adults improved anthropometric and metabolic markers, reduced muscle mass, fT3, GGT, proinflammatory, and CV parameters, and displayed no changes in kidney and pancreas function. The group treated with metformin after the treatment was still more obese and had higher C-reactive protein (CRP) and homeostasis model assessment-an index of insulin resistance (HOMA-IR), but despite this, considerably reduced the number of patients with glucose intolerance.

Effect of Sarcopenia on 10-Year Risk of Atherosclerotic Cardiovascular Disease in Patients with Type 2 Diabetes Mellitus.

To investigate the impact of sarcopenia on the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) among individuals with type 2 diabetes mellitus (T2DM). This study included the clinical, laboratory, and body composition data of 1491 patients with T2DM who were admitted to the Department of Endocrinology and Metabolism at Tianjin Union Medical Center from July 2018 to July 2023. The China-PAR model was utilized to evaluate cardiovascular disease risk. Associations between ASCVD risk and various clinical parameters were analyzed, and the relationship between body composition parameters and ASCVD risk was assessed using logistic regression. The analysis revealed that T2DM patients with sarcopenia had a higher 10-year ASCVD risk compared to those without sarcopenia, with reduced muscle mass independently predicting an increased risk of cardiovascular disease. This association was significant among female T2DM patients, while male T2DM patients with sarcopenia showed a marginally higher median ASCVD risk compared to their non-sarcopenic counterparts. ASCVD risk inversely correlated with body muscle parameters and positively correlated with fat content parameters. Specifically, height- and weight-adjusted fat mass (FM, FM%, FMI) were identified as risk factors for ASCVD. Conversely, muscle parameters adjusted for weight and fat (ASM%, SMM%, FFM%, ASM/FM, SMM/FM, FMM/FM) were protective against ASCVD risk. These findings highlight the critical role of sarcopenia in influencing cardiovascular disease risk among Chinese patients with T2DM, as predicted by the China-PAR model. This study highlights the importance of sarcopenia in T2DM patients, not only as an indicator of ASCVD risk, but possibly as an independent risk factor in this demographics.

EFFETS DE LASSOCIATION DE LEXERCICE PHYSIQUE ET DU MASSAGE SUEDOIS SUR LA SCIATALGIE CHEZ LES FEMMES DE YAOUNDE (CAMEROUN)

Background: Sciatica is a common chronic musculoskeletal disorder among women in developing countries. However, management strategies for this condition in these regions are often inadequate. Objective: The aim of this study was to evaluate the effectiveness of a therapeutic programme combining Swedish massage and physical exercise on the symptoms of sciatica in women in the city of Yaounde in Cameroun. Methodology : This was a cross-sectional study of 30 women suffering from sciatica. The women were divided equally into three groups. The first (G1) was made up of women who only took physical exercise, the second (G2) of those who only received Swedish massage sessions and the third (G3) of those who received both physical exercise and Swedish massage. Results : The results show an overall decrease in anthropometric parameters. This decline was most marked in G3 (ΔG3 = -3.21%) and G1 (ΔG1 = -10.10%), for body mass and bone mass respectively. G2 showed the greatest reductions in water mass (ΔG2 = -16.97%), fat mass (ΔG2 = -21.19%) and muscle mass (ΔG2 = -8.76%). The results then show an overall improvement in pain parameters. This observation was more marked in G2, irrespective of the parameter considered. On the other hand, G1 showed the best result for pain at the present time (ΔG1 = -73.57%), while G2 showed the greatest improvements for usual pain (ΔG3 = -52.24%) and most intense pain (ΔG3 = -64.06%). Finally, the results indicate an overall reduction in the consequences of pain. This reduction was more marked in G2, but G3 showed the best results in terms of social relationships. Conclusion : In conclusion, physical exercise and Swedish massage promoted remission of most of the symptoms of sciatica in the subjects studied, especially when these two methods were combined.

An Observational Study of Nutritional Assessment, Prescription, Practices, and Its Outcome among Critically Ill Patients Admitted to an Intensive Care Unit.

Optimal feeding strategy for critically ill patients of intensive care unit (ICU) is often a matter of debate as patients admitted to ICU are highly catabolic and reduction in muscle mass is very common. We aimed at early achievement of nutritional goals in preventing skeletal muscle breakdown and improving clinical outcomes among critically ill patients with high risk of malnutrition. Nutrition risk in the critically ill (mNUTRIC) Score was used to identify the risk of malnutrition within 24 hours of admission. Quadriceps muscle mass index was measured within 24 hours of admission to ICU and repeated on 7th day. Enteral feeding was monitored by the nutrition expert as part of routine patient care and clinical outcomes were monitored. A total of 287 patients admitted in ICU were screened for malnutrition and 60 (20.9%) of them had high score (>5). There was no statistically significant reduction in the quadriceps muscle mass index (p < 0.05) (t = 0.601) measured within 24 hours of admission and on the 7th day of ICU stay, signifying that the nutritional prescription and monitoring may be useful in preserving the muscle mass. This study did not find statistically significant association between the high mNUTRIC score on admission and the clinical outcomes, such as 28 days mortality, incidence of pressure ulcers, length of ICU stay, and hospital-acquired infection (p > 0.05). Early initiation and maintenance of enteral nutrition is essential for meeting target calories and protein requirements. It may help to preserve muscle mass in critically ill patients who are otherwise at high risk of malnutrition. Sharon T, Nayak SG, Shanbhag V, Hebbar S. An Observational Study of Nutritional Assessment, Prescription, Practices, and Its Outcome among Critically Ill Patients Admitted to an Intensive Care Unit. Indian J Crit Care Med 2024;28(4):364-368.

The effect of low birth weight as an intrauterine exposure on the early onset of sarcopenia through possible molecular pathways.

Sarcopenia, a musculoskeletal disease characterized by the progressive loss of skeletal muscle mass, strength, and physical performance, presents significant challenges to global public health due to its adverse effects on mobility, morbidity, mortality, and healthcare costs. This comprehensive review explores the intricate connections between sarcopenia and low birth weight (LBW), emphasizing the developmental origins of health and disease (DOHaD) hypothesis, inflammatory processes (inflammaging), mitochondrial dysfunction, circadian rhythm disruptions, epigenetic mechanisms, and genetic variations revealed through genome-wide studies (GWAS). A systematic search strategy was developed using PubMed to identify relevant English-language publications on sarcopenia, LBW, DOHaD, inflammaging, mitochondrial dysfunction, circadian disruption, epigenetic mechanisms, and GWAS. The publications consist of 46.2% reviews, 21.2% cohort studies, 4.8% systematic reviews, 1.9% cross-sectional studies, 13.4% animal studies, 4.8% genome-wide studies, 5.8% epigenome-wide studies, and 1.9% book chapters. The review identified key factors contributing to sarcopenia development, including the DOHaD hypothesis, LBW impact on muscle mass, inflammaging, mitochondrial dysfunction, the influence of clock genes, the role of epigenetic mechanisms, and genetic variations revealed through GWAS. The DOHaD theory suggests that LBW induces epigenetic alterations during foetal development, impacting long-term health outcomes, including the early onset of sarcopenia. LBW correlates with reduced muscle mass, grip strength, and lean body mass in adulthood, increasing the risk of sarcopenia. Chronic inflammation (inflammaging) and mitochondrial dysfunction contribute to sarcopenia, with LBW linked to increased oxidative stress and dysfunction. Disrupted circadian rhythms, regulated by genes such as BMAL1 and CLOCK, are associated with both LBW and sarcopenia, impacting lipid metabolism, muscle mass, and the ageing process. Early-life exposures, including LBW, induce epigenetic modifications like DNA methylation (DNAm) and histone changes, playing a pivotal role in sarcopenia development. Genome-wide studies have identified candidate genes and variants associated with lean body mass, muscle weakness, and sarcopenia, providing insights into genetic factors contributing to the disorder. LBW emerges as a potential early predictor of sarcopenia development, reflecting the impact of intrauterine exposures on long-term health outcomes. Understanding the complex interplay between LBW with inflammaging, mitochondrial dysfunction, circadian disruption, and epigenetic factors is essential for elucidating the pathogenesis of sarcopenia and developing targeted interventions. Future research on GWAS and the underlying mechanisms of LBW-associated sarcopenia is warranted to inform preventive strategies and improve public health outcomes.

Matrix mechanics regulates muscle regeneration by modulating kinesin-1 activity

Sarcopenia, a prevalent muscle disease characterized by muscle mass and strength reduction, is associated with impaired skeletal muscle regeneration. However, the influence of the biomechanical properties of sarcopenic skeletal muscle on the efficiency of the myogenic program remains unclear. Herein, we established a mouse model of sarcopenia and observed a reduction in stiffness within the sarcopenic skeletal muscle in vivo. To investigate whether the biomechanical properties of skeletal muscle directly impact the myogenic program, we established an in vitro system to explore the intrinsic mechanism involving matrix stiffness control of myogenic differentiation. Our findings identify the microtubule motor protein, kinesin-1, as a mechano-transduction hub that senses and responds to matrix stiffness, crucial for myogenic differentiation and muscle regeneration. Specifically, kinesin-1 activity is positively regulated by stiff matrices, facilitating its role in transporting mitochondria and enhancing translocation of the glucose transporter GLUT4 to the cell surface for glucose uptake. Conversely, the softer matrices significantly suppress kinesin-1 activity, leading to the accumulation of mitochondria around nuclei and hindering glucose uptake by inhibiting GLUT4 membrane translocation, consequently impairing myogenic differentiation. The insights gained from the in-vitro system highlight the mechano-transduction significance of kinesin-1 motor proteins in myogenic differentiation. Furthermore, our study confirms that enhancing kinesin-1 activity in the sarcopenic mouse model restores satellite cell expansion, myogenic differentiation, and muscle regeneration. Taken together, our findings provide a potential target for improving muscle regeneration in sarcopenia.