Age-related Loss Of Muscle Mass Research Articles

Effects of the Vitality Acupunch Exercise Program on Older Adults With Probable Sarcopenia: A Mixed Methods Pilot Study.

Purpose: Age-related loss of muscle mass and strength is a highly prevalent condition in older adults in long-term care (LTC) facilities. This pilot study aimed to test the effects of a vitality acupunch (VA) exercise program on muscle mass, muscle strength, muscle endurance, functional fitness, activities of daily living, quality of life, and sleep quality of older adults in LTC facilities with probable sarcopenia in the United States and understand the experiences of residents who participated in the VA program. Design: A mixed-methods experimental design was used for this study. Methods: The quantitative phase included a sample of 27 participants randomly assigned to the control (n = 13) or VA (n = 14) condition. The VA condition consisted of three weekly 40-minute instructor-led seated exercise sessions over 24 weeks. Measures were obtained at baseline, three, and sixmonth intervals. Semi-structured interviews were conducted to explore participant's experiences of the program. Findings: Statistical comparison revealed significantly higher handgrip strength for the VA group (p = .008). Narrative analysis revealed that the program had a positive impact on participant's daily lives. Conclusions: The VA program offers a holistic, evidence-based exercise program for older adults with probable sarcopenia living in LTC facilities.

Ageing leads to selective type II myofibre deterioration and denervation independent of reinnervative capacity in human skeletal muscle.

Age-related loss of muscle mass and function is underpinned by changes at the myocellular level. However, our understanding of the aged muscle phenotype might be confounded by factors secondary to ageing per se, such as inactivity and adiposity. Here, using healthy, lean, recreationally active, older men, we investigated the impact of ageing on myocellular properties in skeletal muscle. Muscle biopsies were obtained from young men (22±3years, n=10) and older men (69±3years, n=11) matched for health status, activity level and body mass index. Immunofluorescence was used to assess myofibre composition, morphology (size and shape), capillarization, the content of satellite cells and myonuclei, the spatial relationship between satellite cells and capillaries, denervation and myofibre grouping. Compared with young muscle, aged muscle contained 53% more type I myofibres, in addition to smaller (-32%) and misshapen (3%) type II myofibres (P<0.05). Aged muscle manifested fewer capillaries (-29%) and satellite cells (-38%) surrounding type II myofibres (P<0.05); however, the spatial relationship between these two remained intact. The proportion of denervated myofibres was ∼2.6-fold higher in old than young muscle (P<0.05). Aged muscle had more grouped type I myofibres (∼18-fold), primarily driven by increased size of existing groups rather than increased group frequency (P<0.05). Aged muscle displayed selective deterioration of type II myofibres alongside increased denervation and myofibre grouping. These data are key to understanding the cellular basis of age-related muscle decline and reveal a pressing need to fine-tune strategies to preserve type II myofibres and innervation status in ageing populations.

Prognostic Value of Sarcopenia in Elderly Patients with Metastatic Non-Small-Cell Lung Cancer Undergoing Radiotherapy

Background: Sarcopenia, a syndrome characterized by age-related loss of muscle mass and function, lacks universally accepted diagnostic criteria, particularly for its role as a prognostic factor in elderly patients with non-small-cell lung cancer (NSCLC). This study aimed to evaluate the prognostic significance of sarcopenia, assessed by psoas muscle size on baseline CT scans, in patients over 70 years of age with metastatic NSCLC. Methods: We retrospectively analyzed 85 elderly patients undergoing palliative radiation therapy between August 2022 and July 2024. Using morphometric analysis of psoas size, we investigated its correlation with overall survival (OS) and progression-free survival (PFS). Results: Our results showed that decreased psoas size was significantly associated with shorter OS and PFS, with median OS of 10 months and PFS of 4 months in sarcopenic patients compared to longer survival times in non-sarcopenic patients. Median survival of non-sarcopenic vs. sarcopenic patients was 21 ± 7 months (muscle area &gt; median) versus 5 ± 2.3 months (muscle area &lt; median). Multivariate analysis confirmed that psoas size, along with ECOG performance status and treatment of primary NSCLC, was a significant predictor of survival. Discussion: These findings suggest that psoas muscle size is a valuable prognostic marker for elderly NSCLC patients, potentially guiding treatment decisions and patient management. Further research is needed to validate these results and refine prognostic models for this population.

Exploring the relationship between sarcopenia and 11 respiratory diseases: a comprehensive mendelian randomization analysis

BackgroundSarcopenia (SP) is an aging-related loss of muscle mass and function, affecting the respiratory system. However, the causality of the association between sarcopenia on lung diseases remains elusive.MethodsThe bidirectional univariate Mendelian randomization (UVMR), multivariate MR (MVMR) analysis, and mediation MR were utilized to systematically investigate the genetic causal relationship of SP and 11 respiratory diseases. Independent genomic variants related to sarcopenia or respiratory diseases were identified as instrumental variables (IVs), and the summary level data of genome-wide associated studies (GWAS) were obtained from the UK biobank and FinnGen. MVMR analysis was conducted to explore the mediation effects of body mass index (BMI), Alcohol Use Disorders Identification Test (AUDIT), smoking, education attainment (EA), physical activity, and Type 2 Diabetes Mellitus (T2DM).ResultsForward UVMR analysis based on the primary method revealed that pneumoconiosis was associated with a higher risk of appendicular lean mass (ALM) (OR = 1.01, p = 0.03), and BMI (10.65%), smoking (10.65%), and physical activity (17.70%) had a mediating role in the effect of pneumoconiosis on ALM. In reverse MR analysis, we found that genetically predicted ALM was significantly associated with an increased risk of pulmonary embolism (PE) (OR = 1.24, p = 7.21E-05). Chronic obstructive pulmonary disease (COPD) (OR = 0.98, p = 0.002) and sarcoidosis (OR = 1.01, p = 0.004) were identified to increase the loss of left-hand grip strength (HGS). Conversely, the increase in left- HGS presented a protective effect on chronic bronchitis (CB) (OR = 0.35, p = 0.03), (OR = 0.80, p = 0.02), and asthma (OR = 0.78, p = 0.04). Similarly, the loss of the right-HGS elevated the risk of low respiratory tract infection (LRTI) (OR = 0.97, p = 0.02) and bronchiectasis (OR = 1.01, p = 0.03), which is also an independent protective factor for LRTI and asthma. In the aspects of low HGS, the risk of LRTI was increased after MVMR analysis, and the risk of sarcoidosis and pneumoconiosis was elevated in the reverse analysis. Lastly, asthma was found to be related to the loss of the usual walking pace, and the reverse MR analysis suggested a causal relationship between the usual walking pace and LRTI (OR = 0.32, p = 2.79 × 10−5), asthma (OR = 0.24, p = 2.09 × 10−6), COPD (OR = 0.22, p = 6.64 × 10−4), and PE(OR = 0.35, p = 0.03).ConclusionsThis data-driven MR analysis revealed SP was bidirectional causally associated with lung diseases, providing genetic evidence for further mechanistic and clinical studies to understand the crosstalk between SP and lung diseases.

Examination of Sarcopenia with Obesity as a Prognostic Factor in Patients with Colorectal Cancer Using the Psoas Muscle Mass Index

Background: Sarcopenia, the age-related loss of muscle mass, is a negative prognostic factor in gastrointestinal cancer. Sarcopenia combined with visceral obesity (sarcopenic obesity) is associated with poor outcomes. We explored the influence of obesity and other factors on the prognosis of patients with colorectal cancer diagnosed with sarcopenia. Methods: We enrolled 211 patients with colorectal cancer diagnosed with preoperative sarcopenic obesity who underwent radical resection at Osaka University Hospital between January 2009 and January 2012. Muscle mass was assessed using the psoas muscle mass index. Obesity was evaluated by measuring the visceral fat area in the umbilical region. Patients were categorized into two groups: sarcopenia with obesity (SO) and sarcopenia without obesity (non-SO). Overall survival, cancer-specific survival, and cancer-related relapse-free survival (CRRFS) were compared between the two groups. Patient characteristics, including age, sex, body mass index, serum albumin, C-reactive protein, tumor markers, prognostic nutritional index (PNI), modified Glasgow prognostic score (mGPS), and geriatric nutritional risk index (GNRI), were also analyzed. Results: CRRFS was significantly shorter in the SO group than in the non-SO group (p = 0.028). PNI, mGPS, and GNRI were not identified as significant prognostic factors for CRRFS. Multivariate analysis highlighted sarcopenic obesity, elevated carcinoembryonic antigen levels, and unfavorable histological types as significant predictors of poor CRRFS outcomes. Conclusions: Sarcopenic obesity is an independent predictor of poor prognosis in patients with CRC. Thus, interventions aimed at increasing muscle mass and reducing visceral fat could potentially improve the prognosis of these patients.

Prevalence and factors associated with sarcopenia among urban and rural Indian adults in middle age: A cross-sectional study from Western India.

Sarcopenia is the age-related loss of muscle mass and function. India has 8.6% of the global elderly (>60 years) population, and this is expected to increase to 20% by 2050. Around 70% of Indians live in rural areas where lifestyle factors like diet and physical activity differ from urban areas. Understanding age, sex and location-specific sarcopenia prevalence in India is crucial. Thus, our aim was to assess the prevalence and determinants of sarcopenia in urban and rural community-dwelling men and women aged 40 years and older, representing the next generation of older Indian adults. This cross-sectional study included 745 adults (400 women) from urban and rural areas near Pune, Western India. Assessments included socio-demography, diet by-24-hr recall, physical activity, anthropometry (height, weight), muscle mass measurement by dual-energy X-ray absorptiometry, muscle strength (hand grip) & muscle function by Short Physical Performance Battery (SPPB). Sarcopenia was defined by Asian Working Group on Sarcopenia-2019 guidelines Mean age of participants was 53±7.6yrs. Overall prevalence of sarcopenia was 10% and of severe sarcopenia was 4.2%. Sarcopenia prevalence was higher in rural (14.8%) than urban (6.8%) participants and in men (12.5%) than women (8%, all p<0.05). Muscle mass, grip strength and SPPB score were all higher in urban than rural participants (p<0.05). Older age, rural residence, inadequate protein intake, and lower socio-economic status were independently associated with sarcopenia. In this middle-aged group, sarcopenia prevalence was similar to that observed in older Western populations, over 100% higher among rural than urban participants, and higher amongst men than women. Age, location, protein intake and socioeconomic status were factors associated with sarcopenia. Given this rapidly increasing population of older adults in India there is an urgent need to plan strategies for early sarcopenia diagnosis and management, especially in rural populations.

Submaximal eccentric resistance training increases serial sarcomere number and improves dynamic muscle performance in old rats.

The age-related loss of muscle mass is partly accounted for by the loss of sarcomeres in series, contributing to declines in muscle mechanical performance. Resistance training biased to eccentric contractions increases serial sarcomere number (SSN) in young muscle, however, maximal eccentric training in old rats previously did not alter SSN and worsened performance. A submaximal eccentric training stimulus may be more conducive to adaptation for aged muscle. The purpose of this study was to assess whether submaximal eccentric training can increase SSN and improve mechanical function in old rats. Twelve 32-month-old male F344/BN rats completed 4 weeks of submaximal (60% maximum) eccentric plantar-flexion training 3 days/week. Pre- and post-training, we assessed in-vivo maximum isometric torque at a stretched and neutral ankle angle, the passive torque-angle relationship, and the isotonic torque-velocity-power relationship. The soleus and medial gastrocnemius (MG) were harvested for SSN measurements via laser diffraction, with the untrained leg as a control. SSN increased 11% and 8% in the soleus and MG, respectively. Training also shifted optimal torque production towards longer muscle lengths, reduced passive torque 42%, and increased peak isotonic power 23%. Submaximal eccentric training was beneficial for aged muscle adaptations, increasing SSN, reducing muscle passive tension, and improving dynamic contractile performance.

Unacylated Ghrelin Protects Against Age-Related Loss of Muscle Mass and Contractile Dysfunction in Skeletal Muscle.

Sarcopenia, the progressive loss of muscle mass and function, universally affects older adults and is closely associated with frailty and reduced quality of life. Despite the inevitable consequences of sarcopenia and its relevance to healthspan, no pharmacological therapies are currently available. Ghrelin is a gut-released hormone that increases appetite and body weight through acylation. Acylated ghrelin activates its receptor, growth hormone secretagogue receptor 1a (GHSR1a), in the brain by binding to it. Studies have demonstrated that acyl and unacylated ghrelin (UnAG) both have protective effects against acute pathological conditions independent of receptor activation. Here, we investigated the long-term effects of UnAG in age-associated muscle atrophy and contractile dysfunction in mice. Four-month-old and 18-month-old mice were subjected to either UnAG or control treatment for 10 months. UnAG did not affect food consumption or body weight. Gastrocnemius and quadriceps muscle weights were reduced by 20%-30% with age, which was partially protected against by UnAG. Specific force, force per cross-sectional area, measured in isolated extensor digitorum longus muscle was diminished by 30% in old mice; however, UnAG prevented the loss of specific force. UnAG also protected from decreases in mitochondrial respiration and increases in hydrogen peroxide generation of skeletal muscle of old mice. Results of bulk mRNA-seq analysis and our contractile function data show that UnAG reversed neuromuscular junction impairment that occurs with age. Collectively, our data revealed the direct role of UnAG in mitigating sarcopenia in mice, independent of food consumption or body weight, implicating UnAG treatment as a potential therapy against sarcopenia.

The association between non‑high‑density lipoprotein cholesterol to high‑density lipoprotein cholesterol ratio (NHHR) and low muscle mass in adults aged 20–59: a population-based study in the United States

BackgroundThe ratio between non-high-density lipoprotein cholesterol and high-density lipoprotein cholesterol (NHHR) is a reliable marker for assessing the risk linked to lipid metabolism disorders. Sarcopenia, characterized by age-related loss of muscle mass and strength/function, includes the assessment of muscle mass, muscle strength, and muscle-specific strength. However, research into NHHR’s relationship with low muscle mass risk remains unexplored.MethodsOur study utilized a cross-sectional approach, examining data derived from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018. Through multivariable linear and logistic regression, we investigated the relationships of the NHHR with muscle mass and low muscle mass. We visualized the results using smoothing curves and assessed threshold effects. We also performed various subgroup and sensitivity analyses.ResultsThis research encompassed 9,012 participants and demonstrated significant nonlinear associations between NHHR and ALMBMI or low muscle mass risk in a generalized additive model (GAM), pinpointing critical NHHR values (3.328 and 3.367) where changes in NHHR significantly impacted ALMBMI and low muscle mass risk.ConclusionsThe NHHR demonstrates a significant association with an increased risk of low muscle mass among middle-aged Americans. This ratio has potential as a predictive marker for low muscle mass. Further exploration of NHHR is expected to aid in advancing preventive and therapeutic measures for this condition.

Bidirectional transitions of sarcopenia states in older adults: The longitudinal evidence from CHARLS.

Sarcopenia, the age-related loss of muscle mass and function, brings multiple adverse outcomes including disability and death. Several sarcopenia consensuses have newly introduced the premorbid concept of possible sarcopenia and recommended early lifestyle interventions. Bidirectional transitions of premorbid states have been revealed in several chronic diseases yet not clarified in sarcopenia. This study aims to investigate the underlying transition patterns of sarcopenia states. The study utilized three waves of data from a nationally representative survey, the China Health and Retirement Longitudinal Study (CHARLS), and included community-dwelling individuals aged 60years and older with at least two sarcopenia states assessments based on the Asian Working Group for Sarcopenia criteria 2019 (AWGS2019) between 2011 and 2015. The estimated transition intensity and probability between non-sarcopenia, possible sarcopenia, sarcopenia, and death were investigated using multi-stage Markov (MSM) models. The study comprised 4395 individuals (49.2% female, median age 67years) with a total of 10778 records of sarcopenia state assessment, and the mean follow-up period was 3.29years. A total of 24.5% of individuals with a current state of possible sarcopenia returned to non-sarcopenia, 60.3% remained possible sarcopenia, 6.7% progressed to sarcopenia, and 8.5% died by the next follow-up. The transition intensity of recovery to non-sarcopenia (0.252, 95% CI 0.231-0.275) was 2.8 times greater than the deterioration to sarcopenia (0.090, 95% CI 0.080-0.100) for individuals with possible sarcopenia. For individuals with possible sarcopenia, the estimated probabilities of recovering to non-sarcopenia, progressing to sarcopenia, and transitioning to death within a 1-year observation were 0.181, 0.066, and 0.035, respectively. For individuals with sarcopenia, the estimated probabilities of recovering to non-sarcopenia, recovering to possible sarcopenia, and transitioning to death within 1-year observation were 0.016, 0.125, and 0.075, respectively. In covariables analysis, age, sex, body mass index, physical function impairment, smoking, hypertension, and diabetes are important factors influencing bidirectional transitions. The findings highlight the bidirectional transitions of sarcopenia states among older adults and reveal a notable proportion of possible sarcopenia show potential for recovery in the natural course. Screening and intensifying interventions based on risk factors may facilitate a recovery transition.

Sex differences in physical functioning among older adults: cross-sectional results from the OUTDOOR ACTIVE study

BackgroundMaintaining good functional ability is a key component of healthy ageing and a basic requirement for carrying out activities of daily living, staying independent, and delaying admission to a nursing home. Even though women have a higher life expectancy and slower age-related muscle mass loss than men, they often show a higher prevalence of limitations in physical functioning. However, the reasons behind these sex differences are still unclear. Therefore, the aims of this study were to investigate sex differences among older adults regarding physical functioning and to study which factors are explaining these sex differences.MethodsCross-sectional data from participants of the OUTDOOR ACTIVE study residing in Bremen, Germany, aged 65 to 75 years, were included in the analyses. Physical functioning was assessed via a self-administered questionnaire using the SF-36 10-item Physical Functioning Scale. Social, lifestyle, and health-related factors were also assessed using the questionnaire. Physical activity was measured objectively using wrist-worn accelerometers over seven consecutive days. Descriptive analyses with absolute and relative frequencies, means and standard deviations, as well as T-tests and chi-square tests were carried out. To test for associations between sex, physical functioning, and several individual factors, linear regressions were performed.ResultsData of 2 141 participants (52.1% female) were included in the study. Women and men showed statistically significant differences in physical functioning, with men perceiving fewer limitations than women. On average, women had a physical functioning score of 81.4 ± 19.3 and men 86.7 ± 17.0. Linear regression showed a statistically significant negative association between physical functioning score and sex (β: -0.15, 95% CL: -0.19, -0.10). The association remained statistically significant when adding individual factors to the model. All factors together were only able to explain 51% of the physical functioning-sex association with health indicators and the presence of chronic diseases being the most influential factors.ConclusionsWe found sex differences in physical functioning, with older women having more limitations than older men. The results showed that health-related factors and chronic diseases played the biggest roles in the different physical functioning scores of women and men. These findings contribute to future longitudinal, more in-depth research.Trial registrationGerman Clinical Trials Register DRKS00015117 (Date of registration 17-07-2018).

Bioinformatics and system biology approach to identify potential common pathogenesis for COVID-19 infection and sarcopenia.

Sarcopenia is a condition characterized by age-related loss of muscle mass and strength. Increasing evidence suggests that patients with sarcopenia have higher rates of coronavirus 2019 (COVID-19) infection and poorer post-infection outcomes. However, the exact mechanism and connections between the two is unknown. In this study, we used high-throughput data from the GEO database for sarcopenia (GSE111016) and COVID-19 (GSE171110) to identify common differentially expressed genes (DEGs). We conducted GO and KEGG pathway analyses, as well as PPI network analysis on these DEGs. Using seven algorithms from the Cytoscape plug-in cytoHubba, we identified 15 common hub genes. Further analyses included enrichment, PPI interaction, TF-gene and miRNA-gene regulatory networks, gene-disease associations, and drug prediction. Additionally, we evaluated immune cell infiltration with CIBERSORT and assessed the diagnostic accuracy of hub genes for sarcopenia and COVID-19 using ROC curves. In total, we identified 66 DEGs (34 up-regulated and 32 down-regulated) and 15 hub genes associated with sarcopenia and COVID-19. GO and KEGG analyses revealed functions and pathways between the two diseases. TF-genes and TF-miRNA regulatory network suggest that FOXOC1 and hsa-mir-155-5p may be identified as key regulators, while gene-disease analysis showed strong correlations with hub genes in schizophrenia and bipolar disorder. Immune infiltration showed a correlation between the degree of immune infiltration and the level of infiltration of different immune cell subpopulations of hub genes in different datasets. The ROC curves for ALDH1L2 and KLF5 genes demonstrated their potential as diagnostic markers for both sarcopenia and COVID-19. This study suggests that sarcopenia and COVID-19 may share pathogenic pathways, and these pathways and hub genes offer new targets and strategies for early diagnosis, effective treatment, and tailored therapies for sarcopenia patients with COVID-19.

Resveratrol impinges on retrograde communication without inducing mitochondrial biogenesis in aged rat soleus muscle

The natural polyphenol resveratrol (RSV) might counteract the skeletal muscle age-related loss of muscle mass and strength/function partly acting on mitochondria. This work analysed the effects of a six-week administration of RSV (50 mg/kg/day) in the oxidative Soleus (Sol) skeletal muscle of old rats (27 months old). RSV effects on key mitochondrial biogenesis proteins led to un unchanged amount of SIRT1 protein and a marked decrease (60 %) in PGC-1α protein. In addition, Peroxyredoxin 3 (PRXIII) protein decreased by 50 %, which on overall suggested the absence of induction of mitochondrial biogenesis by RSV in old Sol. A novel direct correlation between PGC-1α and PRXIII proteins was demonstrated by correlation analysis in RSV and ad-libitum (AL) rats, supporting the reciprocally coordinated expression of the proteins. RSV supplementation led to an unexpected 50 % increase in the frequency of the oxidized base OH8dG in mtDNA. Furthermore, RSV supplementation induced a 50 % increase in the DRP1 protein of mitochondrial dynamics. In both rat groups an inverse correlation between PGC-1α and the frequency of OH8dG as well as an inverse correlation between PRXIII and the frequency of OH8dG were also found, suggestive of a relationship between oxidative damage to mtDNA and mitochondrial biogenesis activity. Such results may indicate that the antioxidant activity of RSV in aged Sol impinged on the oxidative fiber-specific, ROS-mediated, retrograde communication, thereby affecting the expression of SIRT1, PGC-1α and PRXIII, reducing the compensatory responses to the age-related mitochondrial oxidative stress and decline.

Mapping Knowledge Landscapes and Emerging Trends of Sarcopenic Obesity in Older Adults: A Bibliometric Analysis From 2004 to 2023.

Background The prevalence of obesity in combination with sarcopenia, the age-related loss of muscle mass and strength or physical function, is on the rise among adults aged 65 years and older. A significant portion of this demographic now falls under the classification of sarcopenic obesity, a high-risk geriatric syndrome predominantly seen in an aging population vulnerable to compounded complications from both sarcopenia and obesity. It is essential to promptly evaluate the impact of academic research in this field, taking into account factors such as geographical regions, authors, journals, and institutions. Furthermore, exploring current topics and identifying potential areas that could inspire future researchers to conduct additional studies is crucial for advancing overall health in this population. Methodology A search was conducted in the Web of Science Core Collection database to identify English language articles and reviews focusing on sarcopenic obesity in older adults, published between January 1, 2004, and December 31, 2023. Bibliometric analysis was performed using VOSviewer (v.1.6.18) and CiteSpace (v.6.1.R2). Results A total of 985 original English-language articles were collected, consisting of 783 articles and 202 reviews. The volume of research publications in this field has shown significant growth since 2012. The United States leads in contributions, with 239 articles (24.3% of the total) and the highest number of citations at 18,403, along with the highest total link strength. The University of Melbourne in Australia stands out with 25 published articles (2.5% of the total). University of Verona in Italy has the most citations at 9,405, and Monash University in Australia has the highest total link strength at 53. Among prolific authors, John A. Batsis from Duke University is the most productive with 24 articles (2.4% of the total). The journal "Nutrients" has the most articles on sarcopenic obesity in older adults, publishing 54 articles (5.5% of the total). Key topics in this area include sarcopenia, obesity, sarcopenic obesity, and elderly. Recent interventions focus on "nutrition" and "exercise" for sarcopenic obesity in older adults. Conclusions Research on sarcopenic obesity in older adults has seen significant growth on a global scale from 2004 to 2023, indicating a promising area for further study with potential benefits from current advancements. Although academic inquiries have shed light on various aspects of sarcopenic obesityin older adults, there remains a noticeable dearth of clinical research and evidence-based medicine on the effective management of this condition in elderly individuals. Future studies could focus on developing tailored interventions for older adults with sarcopenic obesity.

Kaempferol-Enhanced Migration and Differentiation of C2C12 Myoblasts via ITG1B/FAK/Paxillin and IGF1R/AKT/mTOR Signaling Pathways.

Kaempferol (KMP), a bioactive flavonoid compound found in fruits and vegetables, contributes to human health in many ways but little is known about its relationship with muscle mass. The effect of KMP on C2C12 myoblast differentiation and the mechanisms that might underlie that effect are studied. This study finds that KMP (1, 10µM) increases the migration and differentiation of C2C12 myoblasts in vitro. Studying the possible mechanism underlying its effect on migration, the study finds that KMP activates Integrin Subunit Beta 1 (ITGB1) in C2C12 myoblasts, increasing p-FAK (Tyr398) and its downstream cell division cycle 42 (CDC42), a protein previously associated with cell migration. Regarding differentiation, KMP upregulates the expression of myosin heavy chain (MHC) and activates IGF1/AKT/mTOR/P70S6K. Interestingly, pretreatment with an AKT inhibitor (LY294002) and siRNA knockdown of IGF1R leads to a decrease in cell differentiation, suggesting that IGF1/AKT activation is required for KMP to induce C2C12 myoblast differentiation. Together, the findings suggest that KMP enhances the migration and differentiation of C2C12 myoblasts through the ITG1B/FAK/paxillin and IGF1R/AKT/mTOR pathways. Thus, KMP supplementation might potentially be used to prevent or delay age-related loss of muscle mass and help maintain muscle health.

The role of sarcopenia in fragility fractures of the pelvis – is sarcopenia an underestimated risk factor?

BackgroundFragility fractures of the pelvis (FFPs) represent a significant health burden, particularly for the elderly. The role of sarcopenia, an age-related loss of muscle mass and function, in the development and impact of these fractures is not well understood. This study aims to investigate the prevalence and impact of osteoporosis and sarcopenia in patients presenting with FFPs.MethodsThis retrospective study evaluated 140 elderly patients with FFPs. The diagnosis of sarcopenia was assessed by psoas muscle area (PMA) and the height-adjusted psoas muscle index (PMI) measured on computed tomography (CT) scans. Clinical data, radiological findings and functional outcomes were recorded and compared with the presence or absence of sarcopenia and osteoporosis.ResultsOur study cohort comprised 119 female (85.0%) and 21 (15.0%) male patients. The mean age at the time of injury or onset of symptoms was 82.26 ± 8.50 years.Sarcopenia was diagnosed in 68.6% (n = 96) patients using PMA and 68.8% (n = 88) using PMI. 73.6% (n = 103) of our study population had osteoporosis and 20.0% (n = 28) presented with osteopenia. Patients with sarcopenia and osteoporosis had longer hospital stays (p < 0.04), a higher rate of complications (p < 0.048) and functional recovery was significantly impaired, as evidenced by a greater need for assistance in daily living (p < 0.03). However, they were less likely to undergo surgery (p < 0.03) and the type of FFP differed significantly (p < 0.04). There was no significant difference in mortality rate, pre-hospital health status, age or gender.ConclusionOur study highlights the important role of sarcopenia in FFPs in terms of the serious impact on health and quality of life in elderly patients especially when osteoporosis and sarcopenia occur together.Identifying and targeting sarcopenia in older patients may be an important strategy to reduce pelvic fractures and improve recovery. Further research is needed to develop effective prevention and treatment approaches that target muscle health in the elderly.

Musculoskeletal Failure.

Osteoarthritis, osteoporosis, and sarcopenia are prevalent musculoskeletal disorders that significantly impact the aging population's health and quality of life. Osteoarthritis, characterized by joint inflammation, leads to pain, stiffness, and reduced mobility. Osteoporosis, a condition marked by bone density loss, increases fracture susceptibility, especially in postmenopausal women and older adults. Sarcopenia, the age-related loss of muscle mass and function, contributes to frailty and an increased risk of falls. Combined, osteoarthritis, osteoporosis and sarcopenia constitute "Musculoskeletal Failure." These 3 conditions share common risk factors like aging, genetics, and hormonal changes, as well as unhealthy lifestyle behaviors resulting in systemic chronic inflammation. Healthy lifestyle behaviors, including regular physical activity and a nutritious diet across the lifespan play a crucial role in the prevention and management of musculoskeletal failure. Awareness of the relationship between lifestyle behaviors, systemic chronic inflammation and the development and progression of these 3 common conditions is a key step in prevention, early detection and are essential for addressing the complex interplay of these musculoskeletal disorders. As the global population ages, understanding and effectively preventing and managing osteoarthritis, osteoporosis, and sarcopenia become paramount for promoting healthy aging and mitigating the societal and economic burden associated with these conditions.

GCPII Inhibition in Macrophages Delays Age-related Muscle Atrophy in Mice

Age-related loss of muscle mass and strength (Sarcopenia) significantly impairs quality of life in the elderly, yet lacks effective treatments. We previously demonstrated that inhibition of GCPII delayed muscle function decline and neuromuscular junction (NMJ) denervation in an amyotrophic lateral sclerosis (ALS) animal model. As sarcopenia shares NMJ deterioration with ALS, we tested the potent GCPII inhibitor 2-(phosphonomethyl)-pentanedioic acid (2-PMPA) in aging mice, and found that it also preserved muscle function and NMJ integrity. By immunofluorescent staining, we demonstrated that aged mice muscles were associated with GCPII-positive infiltrating macrophages. We next developed a macrophage-targeting GCPII inhibitor delivery system by covalently attaching 2-PMPA to 4th-generation polyamidoamine (G4-PAMAM) dendrimers (D-2-PMPA). The D-2-PMPA was found to inhibit GCPII with IC50= 3.50±0.05 nM. Aged mice muscle showed increased GCPII activity specifically in CD11b+ enriched macrophage cells (138.6±3.0 vs. 336.6±52.9; p&lt;0.05) but not in CD11b− cells. Systemic D-2-PMPA therapy (20 mg/kg 2-PMPA equivalent; IP 3 × /week) completely inhibited the elevated GCPII activity (336.5±52.8 vs. 21.8±9.2 fmol/mg/h; p&lt;0.001). 5-months of D-2-PMPA therapy initiated with 15-month-old mice significantly preserved calf muscle volume (95.0±0.8% vs. 90.4±0.7%; p &lt;0.001), enhanced isometric force (230.2±13.3 vs. 184.0±9.0 mN, female p&lt;0.05; 257.3±21.0 vs. 189.7±19.3 mN, male p&lt;0.05), improved grip strength (96.1±1.6 vs. 90.2±2.2 % of maximum p&lt;0.001) and increased rotarod latency (119.0±6.6 vs. 93.5±9.3 s, female p&lt;0.05; 104.5±5.2 vs. 79.3±4.2 s, male p&lt;0.001). Age-related decline of nerve signal conductivity to muscles was also delayed with D-2-PMPA as observed by improved compound muscle action potential (CMAP) latency (1.28±0.02 vs. 1.38±0.04 ms; p&lt; 0.05) and amplitude (15.2±0.5 vs. 1.27±0.6 mV; p&lt;0.01). Furthermore, NMJ integrity was preserved with treatment as demonstrated by single fiber jitter (5.4±0.3 vs. 7.5±0.5 μs; p&lt;0.01). Overall, our current results support that excessive GCPII activity in muscle macrophages is associated with age-related muscle atrophy, which is improved by GCPII inhibition. This study highlights GCPII inhibition in macrophages as a new therapeutic approach to delay sarcopenia. R01AG078181, R01AG068130, R01NS093416. 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.

Clinical meaning of sarcopenia in patients undergoing endoscopic treatment.

With increasing global life expectancy, the significance of geriatric assessment parameters has increased. Sarcopenia is a crucial assessment parameter and is defined as the age-related loss of muscle mass and strength. Sarcopenia is widely acknowledged as a risk factor for postoperative complications in diverse advanced malignancies and has a detrimental effect on the long-term prognosis. While most studies have primarily concentrated on the correlation between sarcopenia and advanced cancer, more recent investigations have focused on the relationship between sarcopenia and early-stage cancer. Endoscopic submucosal dissection (ESD), which is less invasive than surgical intervention, is extensively employed in the management of early-stage cancer, although it is associated with complications such as bleeding and perforation. In recent years, several reports have revealed the adverse consequences of sarcopenia in patients with early-stage cancer undergoing ESD. This literature review briefly summarizes the recent studies on the association between sarcopenia and ESD.

A New Challenge in Treatment of Sarcopenic Obesity in Older Adults: A Systematic Review

Introduction: Sarcopenic obesity (SO) defined as a phenotype of coexistence of sarcopenia, is an age-related loss of muscle mass and strength or physical performance, and obesity. It is crucial to determine the best management strategy for sarcopenic obese patients in order to improve life expectancy. The goal of this review is to provide an overview of sarcopenic obesity treatment for older persons. Methods: PubMed searches were conducted for ‘sarcopenic obesity treatment’ and ‘sarcopenic obesity elderly treatment’ from a database through the past 10 years. All articles available in English identified by these searches were then reviewed in detail Result: At present, the optimal treatment of sarcopenic has not been established. Nutritional interventions, such as a hypocaloric diet, and exercise training or physical therapy are the mainstay of SO prevention and treatment to achieve changes in body composition (muscle gain and fat reduction) and improve the functional status and quality of life of elderly patients. Conclusion: To further our understanding of SO, it is essential that clinicians and researchers establish a universal consensus for the definition and diagnosis of SO and focus on SO treatment and promote healthy aging. &#x0D; &#x0D; Keywords: sarcopenic obesity, elderly, treatment