Treatment Of Sarcopenia Research Articles

Gut microbiota as a promising therapeutic target for age-related sarcopenia.

Sarcopenia is characterized by a progressive loss of skeletal muscle mass and function with aging. Recently, sarcopenia has been shown to be closely related with gut microbiota. Strategies such as probiotics and fecal microbiota transplantation have shown potential to ameliorate the muscle loss. This review will focus on the age-related sarcopenia, in particular on the relationship between gut microbiota and age-related sarcopenia, how gut microbiota is engaged in sarcopenia, and the potential role of gut microbiota in the treatment of age-related sarcopenia.

The Prevalence of Sarcopenia among Hunan Province Community-Dwelling Adults Aged 60 Years and Older and Its Relationship with Lifestyle: Diagnostic Criteria from the Asian Working Group for Sarcopenia 2019 Update.

Background and Objectives: This study aims to detect the prevalence of sarcopenia in community-dwelling older adults in Hunan Province, discuss factors related to lifestyle, and provide a reliable basis for the prevention and treatment of sarcopenia. Materials and Methods: In this study, a total of 1040 community-dwelling adults ≥ 60 years were examined for sarcopenia using a cluster stratified random sampling method, which was defined using the diagnostic criteria recommended by the Asian Working Group for Sarcopenia (AWGS) from September 2019 to March 2020. Multivariate logistic regression analysis was applied to determine the correlation between sarcopenia and smoking, drinking, nutritional status, physical activity, and sleep quality. Results: A total of 27.1% of the older adults were diagnosed with sarcopenia, with rates of 26.2% in men and 25.2% in women. Multiple logistic regression showed that advanced age (OR = 2.480, 95% CI: 1.730, 3.553), the risk of malnutrition (OR = 2.085, 95% CI: 1.440, 3.019), and malnutrition (OR = 1.212, 95% CI: 0.304, 4.834) were risk factors for sarcopenia. No falls in the previous year (OR = 0.616, 95% CI: 1.885, 1.209), normal weight (OR = 0.228, 95% CI: 0.109, 0.475), overweight (OR = 0.030, 95% CI: 0.013, 0.069), moderate physical activity (OR = 0.593, 95% CI: 0.377, 0.933), or high physical activity (OR = 0.417, 95% CI: 0.230, 0.755) were identified as protective factors for sarcopenia. Conclusions: The prevalence of sarcopenia was high among older adults in the community in Hunan Province. In addition, we found that lifestyle is an important factor in sarcopenia.

Portable Digital Monitoring System for Sarcopenia Screening and Diagnosis.

Sarcopenia is a well-known highly prevalent muscle disease that severely impairs overall physical performance in elders, inducing a massive health-related economic burden. The widespread screening, diagnosis and treatment of sarcopenia are pivotal to restrain the disease progression and constrain its societal impact. Simple-to-use, portable, and reliable methods to evaluate sarcopenia are scarce, and sarcopenia-related assessments are typically done in several time-consuming stages. This study presents a portable digital system that enables a simple and intuitive method to evaluate sarcopenia-based on the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) algorithm-including the four Find-Assess-Confirm-Severity (FACS) steps. The system comprises a mobile application (app); two wireless devices: a dynamometer (Gripwise) and a skinfold caliper (Lipowise); and a back-end website. To find cases, the SARC-F questionnaire is applied. To assess sarcopenia, the handgrip strength and the sit-to-stand tests are performed with the Gripwise and an application-embedded stopwatch, respectively. To confirm cases, anthropometric measures are performed, and muscle quantity is estimated with Lipowise. Finally, to assess severity, the app stopwatch grants the gait speed test application, evaluating physical performance. This step-by-step sarcopenia assessment results in a final grading according to the cut-off points of the EWGSOP2 criteria. All data is automatically encrypted and exported into a GDPR-compliant cloud platform, in which healthcare professionals can access and monitor their patients through the internet.

Lipid hydroperoxides and oxylipins are mediators of denervation induced muscle atrophy

Loss of innervation is a key driver of age associated muscle atrophy and weakness (sarcopenia). Our laboratory has previously shown that denervation induced atrophy is associated with the generation of mitochondrial hydroperoxides and lipid mediators produced downstream of cPLA2 and 12/15 lipoxygenase (12/15-LOX). To define the pathological impact of lipid hydroperoxides generated in denervation-induced atrophy in vivo, we treated mice with liproxstatin-1, a lipid hydroperoxide scavenger. We treated adult male mice with 5 mg/kg liproxstain-1 or vehicle one day prior to sciatic nerve transection and daily for 7 days post-denervation before tissue analysis. Liproxstatin-1 treatment protected gastrocnemius mass and fiber cross sectional area (∼40% less atrophy post-denervation in treated versus untreated mice). Mitochondrial hydroperoxide generation was reduced 80% in vitro and by over 65% in vivo by liproxstatin-1 treatment in denervated permeabilized muscle fibers and decreased the content of 4-HNE by ∼25% post-denervation. Lipidomic analysis revealed detectable levels of 25 oxylipins in denervated gastrocnemius muscle and significantly increased levels for eight oxylipins that are generated by metabolism of fatty acids through 12/15-LOX. Liproxstatin-1 treatment reduced the level of three of the eight denervation-induced oxylipins, specifically 15-HEPE, 13-HOTrE and 17-HDOHE. Denervation elevated protein degradation rates in muscle and treatment with liproxstatin-1 reduced rates of protein breakdown in denervated muscle. In contrast, protein synthesis rates were unchanged by denervation. Targeted proteomics revealed a number of proteins with altered expression after denervation but no effect of liproxstain-1. Transcriptomic analysis revealed 203 differentially expressed genes in denervated muscle from vehicle or liproxstatin-1 treated mice, including ER stress, nitric oxide signaling, Gαi signaling, glucocorticoid receptor signaling, and other pathways. Overall, these data suggest lipid hydroperoxides and oxylipins are key drivers of increased protein breakdown and muscle loss associated with denervation induced atrophy and a potential target for sarcopenia intervention.

Trends in Nutrition Research for Sarcopenia: A Bibliometric Analysis.

Sarcopenia is age-related, pathophysiological muscle atrophy. Research regarding nutrition treatment of sarcopenia has developed rapidly, particularly as populations age. We evaluated the development of trends in this field using a bibliometric analysis. Articles up to July 2022 were searched in the Scopus database. Bibliographic information from the selected publications, such as countries, citations, world maps, institutions, authors, journals, and keywords, were converted and analyzed automatically using the “bibliometrix” package in R environment (version 4.2.0). We identified 368 Scopus articles from 1998–2021. According to citation analyses, 27 documents received more than 100 citations. Bibliometric analysis based on the literature included in this study revealed that South Korea (61 publications), United States (50), Japan (35), China (30), and Italy (20) contributed the most publications. Tehran University of Medical Science (19 records, 2.55% of articles) contributed the most publications. The most productive author was Landi, with eight articles (2.17% of articles). The publications were located in 196 journals, with Nutrients having the most publications (30, 8.15% of articles). The curves representing keywords “sarcopenia” and “aged” were the most apparent. Our analysis suggested that global nutrition and sarcopenia-related research increased rapidly from 2001 to 2021, demonstrating that this was a promising area of future research that could benefit from continued advances. Future research may focus on the effects of age and sex as well as intervention effectiveness, particularly exercise and nutrition supplementation.

Inhibition of High-Temperature Requirement Protein A2 Protease Activity Represses Myogenic Differentiation via UPRmt.

Skeletal muscles require muscle satellite cell (MuSC) differentiation to facilitate the replenishment and repair of muscle fibers. A key step in this process is called myogenic differentiation. The differentiation ability of MuSCs decreases with age and can result in sarcopenia. Although mitochondria have been reported to be involved in myogenic differentiation by promoting a bioenergetic remodeling, little is known about the interplay of mitochondrial proteostasis and myogenic differentiation. High-temperature-requirement protein A2 (HtrA2/Omi) is a protease that regulates proteostasis in the mitochondrial intermembrane space (IMS). Mice deficient in HtrA2 protease activity show a distinct phenotype of sarcopenia. To investigate the role of IMS proteostasis during myogenic differentiation, we treated C2C12 myoblasts with UCF101, a specific inhibitor of HtrA2 during differentiation process. A key step in this process is called myogenic differentiation. The differentiation ability of MuSCs decreases with age and can result in sarcopenia. Further, CHOP, p-eIF2α, and other mitochondrial unfolded protein response (UPRmt)-related proteins are upregulated. Therefore, we suggest that imbalance of mitochondrial IMS proteostasis acts via a retrograde signaling pathway to inhibit myogenic differentiation via the UPRmt pathway. These novel mechanistic insights may have implications for the development of new strategies for the treatment of sarcopenia.

Current Approach to the Diagnosis of Sarcopenia in Heart Failure: A Narrative Review on the Role of Clinical and Imaging Assessments.

Sarcopenia has been established as a predictor of poor outcomes in various clinical settings. It is particularly prevalent in heart failure, a clinical syndrome that poses significant challenges to health care worldwide. Despite this, sarcopenia remains overlooked and undertreated in cardiology practice. Understanding the currently proposed diagnostic process is paramount for the early detection and treatment of sarcopenia to mitigate downstream adverse health outcomes.

Different stages of chronic kidney disease are associated with physical performance in adults over 60 years.

Objective:The purpose of this study was to determine the association between different stages of chronic kidney disease (CKD) and sarcopenia and its components in the Chinese older population.MethodsThe study comprised of 2,213 participants aged ≥ 60 years (1,025 men; mean age: 70.7 years) recruited from Shanghai who were invited to participate in a comprehensive geriatric assessment. Sarcopenia was defined according to the AWGS 2019 consensus update on sarcopenia diagnosis criteria. The glomerular filtration rate (GFR) was estimated using the equation that originated from the CKD-EPI equation, the stages of CKD are classified according to the Kidney Disease—Improving Global Outcomes (KDIGO).ResultsThe overall prevalence of sarcopenia was 19.0%, which increased with the severity of CKD. The prevalence of sarcopenia in patients with CKD 3–4 and kidney failure was significantly higher than that in normal and CKD 1–2 (p < 0.05). In logistic regression analysis model, compared with normal and CKD 1 patients, kidney failure was significantly associated with the increased risk of sarcopenia and low grip strength (p < 0.05); CKD 2, CKD 3–4 and kidney failure groups were significantly associated with an increased risk of low walking speed (p < 0.05), respectively; while the association between CKD and muscle mass was not shown.ConclusionsIn our study, only decreased physical performance, as represented by walking speed, was significantly associated with increased CKD severity. This may improve the evidence for the prevention and intervention of sarcopenia in patients with CKD.

Effects of vibration training vs. conventional resistance training among community-dwelling older people with sarcopenia: three-arm randomized controlled trial protocol.

IntroductionSarcopenia is a chronic and progressive disease, which is accompanied by the decline in muscle mass, muscle strength, and physical performance with aging, and it can lead to falls, fracture, and premature death. The prevention and treatment of sarcopenia mainly include exercise therapy and nutritional supplement. Exercise therapy is one of the most potential interventions to prevent and/or delay the progression of sarcopenia. Resistance training (RT), one of the most commonly used exercise types, is widely used in the treatment of sarcopenia, while vibration training (VT) is a prospective strategy for improving sarcopenia in older people. The aim of our study is to compare the effect of VT and RT in older people with sarcopenia on muscle mass, muscle strength, physical performance, blood biomarkers, and quality of life.Methods and analysisOur study is a 12-week, three-arm randomized controlled trial with assessor-blinded. The diagnosis criteria for subject recruitment adopt the guidelines for the Asian Working Group for Sarcopenia. A total of 54 subjects who met the criteria were randomized into one of the following three groups: VT group, RT group, and control group. The VT group and RT group received a 12-week whole-body vibration training and a resistance training program three times every week, respectively. The primary outcome is lower limb muscle strength, and the secondary outcomes include muscle mass, upper limb muscle strength, physical performance, blood biomarkers, and quality of life. We then performed assessments three times, at baseline (0 week), after intervention (12 weeks), and follow-up (24 weeks). The adverse events were also be reported. All outcome measurements were performed by the same researchers. Data were saved in the unified database, and the collected data of all subjects were analyzed by intention-to-treat analysis.Ethics and disseminationThis study was reviewed and approved by the Ethical Committee of Xinhua Hospital Chongming Branch. The findings of the study were authorized in peer-reviewed journals with online access; meanwhile, it will be presented at domestic or international academic congresses.Clinical trial registrationChinese Clinical Trial Registry (ChiCTR2100051178), registered on 15 September 2021.

Advancing our understanding of skeletal muscle across the lifecourse: Protocol for the MASS_Lifecourse study and characteristics of the first 80 participants.

Sarcopenia, the age-related loss of skeletal muscle strength and mass, carries a significant burden for affected individuals. There has been little investigation of sarcopenia using experimental medicine techniques to study human muscle tissue in detail. The aim of the Muscle Ageing Sarcopenia Studies Lifecourse (MASS_Lifecourse) study is to recruit up to 160 participants, equally divided between females and males between ages 45 and 85years for detailed phenotyping of skeletal muscle health. Here we describe the protocol for the study and the characteristics of the first 80 participants. We are recruiting participants from three sources in the north-east of England. Study fieldwork comprises a home visit (or videocall) for consent and assessment of health, cognition, lifestyle, and wellbeing. This is followed by a visit to a clinical research facility for assessment of sarcopenia status and collection of samples including a vastus lateralis muscle biopsy. We produced descriptive statistics for the first 80 participants, including expressing their grip strength relative to normative data in the form of Z-scores. The first 80 participants (53.8% female) covered the target ages, ranging from 48 to 84years. They were regularly physically active, reported good physical function and had a prevalence of sarcopenia (including probable sarcopenia) of 11.3% based on the revised European consensus. Their grip strength was similar to that in the general population, with a mean Z-score of 0.09 standard deviations (95% CI: -1.64, 1.83) above that expected. The MASS_Lifecourse study combines comprehensive health and lifestyle data with a range of biological samples including skeletal muscle. The findings from planned analyses should contribute to improvements in the diagnosis, treatment, and prevention of sarcopenia.

Skeletal muscle oxidative stress and inflammation in aging: Focus on antioxidant and anti-inflammatory therapy.

With aging, the progressive loss of skeletal muscle will have negative effect on multiple physiological parameters, such as exercise, respiration, thermoregulation, and metabolic homeostasis. Accumulating evidence reveals that oxidative stress and inflammation are the main pathological characteristics of skeletal muscle during aging. Here, we focus on aging-related sarcopenia, summarize the relationship between aging and sarcopenia, and elaborate on aging-mediated oxidative stress and oxidative damage in skeletal muscle and its critical role in the occurrence and development of sarcopenia. In addition, we discuss the production of excessive reactive oxygen species in aging skeletal muscle, which reduces the ability of skeletal muscle satellite cells to participate in muscle regeneration, and analyze the potential molecular mechanism of ROS-mediated mitochondrial dysfunction in aging skeletal muscle. Furthermore, we have also paid extensive attention to the possibility and potential regulatory pathways of skeletal muscle aging and oxidative stress mediate inflammation. Finally, in response to the abnormal activity of oxidative stress and inflammation during aging, we summarize several potential antioxidant and anti-inflammatory strategies for the treatment of sarcopenia, which may provide beneficial help for improving sarcopenia during aging.

Effects of nutritional supplement and resistance training for sarcopenia in patients with inflammatory bowel disease: A randomized controlled trial.

Background:Nutritional supplementation and resistance training are broadly recommended as part of the treatment of sarcopenia, but studies that have evaluated interventions in inflammatory bowel disease patients with sarcopenia are lacking. The aim of this study was to evaluate the effects of nutritional supplementation and resistance training for improving height-adjusted appendicular skeletal muscle mass (ASM/H2) and medical indices in patients with inflammatory bowel disease.Methods:This randomized, double-blind, placebo-controlled trial of forty-five participants was performed at Huadong Hospital Affiliated to Fudan University in Shanghai from September 2020 to June 2021. Eligible participants were randomly assigned to receive whey protein (10 g/d) or placebo (10 g/d) for 8 weeks while completing a resistance training program (3 times a week). Data such as ASM/H2 and other medical indices were collected at baseline and at 4 and 8 weeks of intervention.Results:Fifteen participants were allocated to the resistance training and whey protein (RT+WP) group, and thirteen participants were allocated to the resistance training and placebo (RT+placebo) group. The ASM/H2 significantly increased in the RT+WP group after 4 and 8 weeks of intervention, and the ASM/H2 of the RT+WP group was significantly higher than that of the RT+placebo group after 4 and 8 weeks of intervention (F = 1.092, P = .035). Both interventions significantly increased albumin (F = 7.214, P = .003). Hemoglobin and creatinine significantly increased in the RT+WP group (F = 3.592, P = .035; F = 3.922, P = .033, respectively). In addition, a significant group × time interaction was not observed for body mass index, 5-time chair stand test time, 3-metre walk speed, grip strength, waist circumference, hip circumference, or waist-to-hip ratio (P > .05).Conclusions:Nutritional supplementation may be effective in improving sarcopenia, as well as many other physiological indicators during resistance training.

Editorial: The relationship between sarcopenia and metabolic diseases: Its formation mechanism and intervention means

hormone and DHEAS levels in elderly men. If the study is confirmed in a larger population, the results obtained may shift the paradigm of drug intervention strategy of sarcopenia [22] . The Ghrelin secret-promoting agent capromorelin increases weight and muscle mass in older adults and improves walking and stair climbing [23,24] . These data suggest that Ghrelin has a potential therapeutic effect on sarcopenia, but more prospective studies are needed to confirm it. Other drugs, such as metformin, anti-Myostain Activin ⅱ receptor, estrogen, and angiotensin converting enzyme inhibitors, are all being studied for intervention of sarcopenia [21] . Other potential targets include PGC-1A, phosphodiesterase inhibitors (PDE), skeletal muscle stem cells, and gene recombination [21,23,24] .In summary, the research on sarcopenia is still in its exploratory stage, and the pathogenesis of sarcopenia is not well understood. For future studies, it is necessary to enhance the efforts on elucidating the underlying cellular and molecular mechanisms, developing validate biomarkers, improving the accuracy of diagnostic tests, solving the problem of consistency of diagnostic criteria, and designing effective strategies for the prevention and treatment of sarcopenia. The editors thank all authors and reviewers for their scientific contributions.

Malnutrition risk screening: New insights in a new era

Twenty years ago, ESPEN published its "Guidelines for nutritional screening 2002", with the note that these guidelines were based on the evidence available until 2002, and that they needed to be updated and adapted to current state of knowledge in the future. Twenty years have passed, and tremendous progress has been made in the field of malnutrition risk screening. Many screening tools have been developed and validated for different patient groups and different health care settings. Some countries even have introduced mandatory screening for malnutrition at admission to hospital. Yet, changes in society and healthcare require a reflection on current practice and policies regarding malnutrition risk screening. In this opinion paper, we share our perspectives on malnutrition risk screening in the twenty-twenties, addressing the changing and varying profile of the malnourished individual, the goals of screening and screening tools (i.e., preventive or reactive), the construct of malnutrition risk (i.e., screening for risk factors or screening for existing malnutrition), and screening alongside a patient's journey.

Contribution of muscle satellite cells to sarcopenia.

Sarcopenia, a disorder characterized by age-related muscle loss and reduced muscle strength, is associated with decreased individual independence and quality of life, as well as a high risk of death. Skeletal muscle houses a normally mitotically quiescent population of adult stem cells called muscle satellite cells (MuSCs) that are responsible for muscle maintenance, growth, repair, and regeneration throughout the life cycle. Patients with sarcopenia are often exhibit dysregulation of MuSCs homeostasis. In this review, we focus on the etiology, assessment, and treatment of sarcopenia. We also discuss phenotypic and regulatory mechanisms of MuSC quiescence, activation, and aging states, as well as the controversy between MuSC depletion and sarcopenia. Finally, we give a multi-dimensional treatment strategy for sarcopenia based on improving MuSC function.

The beneficial therapeutic effects of plant-derived natural products for the treatment of sarcopenia.

Sarcopenia is an age-related muscle disorder typically associated with a poor quality of life. Its definition has evolved over time, and several underlying causes of sarcopenia in the elderly have been proposed. However, the exact mechanisms involved in sarcopenia, as well as effective treatments for this condition, are not fully understood. The purpose of this article was to conduct a comprehensive review of previous evidence regarding the definition, diagnosis, risk factors, and efficacy of plant-derived natural products for sarcopenia. The methodological approach for the current narrative review was performed using PubMed, Scopus, and Web of Science databases, as well as Google Scholar (up to March 2021) in order to satisfy our objectives. The substantial beneficial effects along with the safety of some plant-derived natural products including curcumin, resveratrol, catechin, soy protein, and ginseng on sarcopenia are reported in this review. Based on clinical studies, nutraceuticals and functional foods may have beneficial effects on physical performance, including handgrip and knee-extension strength, weight-lifting capacity, time or distance travelled before feeling fatigued, mitochondrial function, muscle fatigue, mean muscle fibre area, and total number of myonuclei. In preclinical studies, supplementation with herbs and natural bioactive compounds resulted in beneficial effects including increased plantaris mass, skeletal muscle mass and strength production, increased expression of anabolic factors myogenin, Myf5 and MyoD, enhanced mitochondrial capacity, and inhibition of muscle atrophy and sarcopenia. We found that several risk factors such as nutritional status, physical inactivity, inflammation, oxidative stress, endocrine system dysfunction, insulin resistance, history of chronic disease, mental health, and genetic factors are linked or associated with sarcopenia. The substantial beneficial effects of some nutraceuticals and functional foods on sarcopenia, including curcumin, resveratrol, catechin, soy protein, and ginseng, without any significant side effects, are reported in this review. Plant-derived natural products might have a beneficial effect on various components of sarcopenia. Nevertheless, due to limited human trials, the clinical benefits of plant-derived natural products remain inconclusive. It is suggested that comprehensive longitudinal clinical studies to better understand risk factors over time, as well as identifying a treatment strategy for sarcopenia that is based on its pathophysiology, be undertaken in future investigations.

Diagnostic and prognostic value of the Creatinine/Cystatin C ratio for low muscle mass evaluation among US adults.

BackgroundIdentifying patients with low muscle mass is crucial for the diagnosis of sarcopenia. Although the Creatinine/Cystatin C (Cr/CysC) is recommended as a simplified indicator to identify patients with low muscle mass, its ability to assess muscle mass and predict a poor prognosis has not been validated. We aimed to determine the diagnosis value of Cr/CysC for low muscle mass and examine the association of Cr/CysC with mortality.MethodsIn this cohort study we analyzed data from the National Health and Nutrition Examination Survey from 1999 to 2002. Follow-up was conducted up to December, 2015. Appendicular skeletal mass was calculated based on dual-energy X-ray absorptiometry (DXA) scans. Low muscle mass was defined referring to five international diagnostic criteria. The diagnostic value of Cr/CysC as a replacement indicator of muscle mass was measured using area under the curve, positive percent agreement, negative percent agreement and kappa. Cox proportional hazards regression models were developed to examine the association between Cr/CysC and risk of mortality.ResultsThis cohort study of 3,741 adults comprised 1,823 females (48.73%), with a weighted mean (SE) age of 44.46 (0.43) years. The positive percent agreement of Cr/CysC for the diagnosis of low muscle mass was poor (40.23–58.74%), except for Foundation of the National Institute of Health (FNIH) criteria (80.90–58.97%). But the negative percent agreement of Cr/CysC for the diagnosis of low muscle mass was high (males: 62.15–88.17%; females: 55.26–82.30%). Moreover, the risk of death was reduced by 2% per 0.01 unit increase in Cr/CysC (aHR, 0.98; 95% CI, 0.98–0.99, P < 0.001).ConclusionsCr/CysC performed well not only in identifying non-sarcopenia cases, especially when based on FNIH diagnostic criteria, but also in revealing a positive association with higher risk of mortality. The optimal cut-off values for Cr/CysC were <1.0 in males and <0.8 in females. Expanding the use of Cr/CysC would allow for early and targeted treatment of sarcopenia.

Sarcopenia in chronic advanced liver diseases: A sex-oriented analysis of the literature.

Sarcopenia, defined as progressive and generalized loss of muscle mass and strength, is common in chronic liver disease. It significantly impacts the quality of life and increases the risk of liver-related complications and mortality in cirrhotic patients. Moreover, recent studies showed a negative impact of sarcopenia on patients awaiting liver transplantation (LT), on post-LT outcomes, and on response to hepatocellular carcinoma therapies. Data about the influence of sex on the incidence, prevalence, diagnosis and treatment of sarcopenia in chronic liver diseases are poor and conflicting. The aims of this review of the literature are to define sex differences in sarcopenic cirrhotic patients and to highlight the necessity of a sex stratified analysis in future studies. This analysis of the literature showed that most of the studies are retrospective, with a higher prevalence of sarcopenia in males, probably due to anatomical differences between the sexes. Moreover, diagnostic criteria for sarcopenia are different between studies, as there is not a defined cut-off and, as a consequence, no comparable results. In conclusion, sex seems to have an impact on sarcopenia, and future studies must accurately investigate its role in identifying and treating high-risk patients, reducing the negative impact of sarcopenia on the survival and quality of life of cirrhotic patients.

Molecular Mechanisms of Inflammation in Sarcopenia: Diagnosis and Therapeutic Update.

Sarcopenia is generally an age-related condition that directly impacts the quality of life. It is also related to chronic diseases such as metabolic dysfunction associated with diabetes and obesity. This means that everyone will be vulnerable to sarcopenia at some point in their life. Research to find the precise molecular mechanisms implicated in this condition can increase knowledge for the better prevention, diagnosis, and treatment of sarcopenia. Our work gathered the most recent research regarding inflammation in sarcopenia and new therapeutic agents proposed to target its consequences in pyroptosis and cellular senescence. Finally, we compared dual X-ray absorptiometry (DXA), magnetic resonance imaging (MRI), and ultrasound (US) as imaging techniques to diagnose and follow up on sarcopenia, indicating their respective advantages and disadvantages. Our goal is for the scientific evidence presented here to help guide future research to understand the molecular mechanisms involved in sarcopenia, new treatment strategies, and their translation into clinical practice.

Leucine and perindopril to improve physical performance in people over 70 years with sarcopenia: the LACE factorial RCT

Background Angiotensin-converting enzyme inhibitors and leucine are promising potential treatments for sarcopenia. Neither has yet been tested in adequately powered randomised trials in patients with sarcopenia. Objectives To determine the efficacy of leucine and perindopril in improving physical function in older people with sarcopenia, to evaluate the effect of leucine and perindopril on muscle mass and to evaluate the predictive biomarkers of sarcopenia. Design A placebo-controlled, parallel group, double-blind, randomised 2 × 2 factorial trial. Setting Primary care and geriatric medicine secondary care departments in 14 UK centres. Participants Adults aged ≥ 70 years with low muscle strength and mass, without contraindications to angiotensin-converting enzyme inhibitors and without known diagnosis-specific skeletal myopathy. Interventions Eligible participants were randomised 1 : 1 to receive 4 mg of oral perindopril or a matching placebo and, separately, were randomised 1 : 1 to receive 2.5 g of oral leucine powder or a matching placebo powder taken thrice daily with meals. Randomisation was performed using an interactive web-based randomisation system run independently of the research team to preserve allocation concealment. Main outcome measures The primary outcome was the between-group difference in the Short Physical Performance Battery (SPPB) score over the 12-month follow-up period. Other outcome measures included appendicular muscle mass, EQ-5D (EuroQol-5 Dimensions) quality-of-life score, grip strength, quadriceps strength, 6-minute walk distance, activities of daily living, hip bone mineral density and insulin resistance. All adverse events and falls were recorded. Protein-, DNA (deoxyribonucleic acid)- and RNA (ribonucleic acid)-based biomarkers were collected at baseline and at 3 and 12 months. Results We screened 320 people and randomised 145 participants. Participants had a mean age of 79 (standard deviation 6) years, 78 (54%) were women and the mean SPPB was 7.0 (standard deviation 2.4). The median adherence was lower for perindopril than for placebo (76% vs. 96%; p &lt; 0.001). Perindopril did not improve the primary outcome (adjusted treatment effect –0.1 points, 95% confidence interval –1.2 to 1.0 points). Quality of life was worse in the perindopril group (treatment effect –12 points, 95% confidence interval –21 to –3 points) and more adverse events occurred in the perindopril group (n = 218 vs. n = 165). Falls rates between the groups were similar and other secondary outcomes showed no significant treatment effect. For leucine compared with placebo, median adherence was the same in both groups (76% vs. 76%; p = 0.99). Leucine did not improve the primary outcome (adjusted treatment effect 0.1 point, 95% confidence interval –1.0 to 1.1 points). No significant treatment effect was found for any secondary outcome. There were similar numbers of adverse events and falls in both groups. Limitations The trial did not reach its original recruitment target; this trial alone cannot confidently exclude clinically important effects of either perindopril or leucine. Future work Further exploration of biomarkers predicting response to sarcopenia interventions is warranted. Conclusions Neither perindopril nor leucine improved physical performance or muscle mass in this trial; meta-analysis confirmed the lack of efficacy of both treatments in improving physical performance. Study registration This trial is registered as ISRCTN90094835 and EudraCT 2014-003455-61. The systematic review is registered as PROSPERO CRD42014013398. Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and National Institute for Health and Care Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 9, No. 8. See the NIHR Journals Library website for further project information.