Frontiers in sarcopenia: Advancements in diagnostics, molecular mechanisms, and therapeutic strategies

Molecular Aspects of Medicine, Journal Year: 2024, Volume and Issue: 97, P. 101270 - 101270

Published: April 6, 2024

The onset of sarcopenia is intimately linked with aging, posing significant implications not only for individual patient quality life but also the broader societal healthcare framework. Early and accurate identification a comprehensive understanding its mechanistic underpinnings therapeutic targets paramount to addressing this condition effectively. This review endeavors present cohesive overview recent advancements in research diagnosis. We initially delve into contemporary diagnostic criteria, specifically referencing European Working Group on Sarcopenia Older People (EWGSOP) 2 Asian (AWGS) 2019 benchmarks. Additionally, we elucidate assessment techniques muscle strength, quantity, physical performance, highlighting tools such as grip chair stand test, dual-energy X-ray Absorptiometry (DEXA), bioelectrical impedance analysis (BIA), gait speed, short performance battery (SPPB), while discussing their inherent advantages limitations. Such pave way early unequivocal diagnosis sarcopenia. Proceeding further, provide deep-dive sarcopenia's pathogenesis, offering thorough examination associated signaling pathways like Myostatin, AMP-activated protein kinase (AMPK), insulin/IGF-1 Signaling (IIS), nuclear factor kappa-light-chain-enhancer activated B cells (NF-κB) pathways. Each pathway's role mediation detailed, underscoring potential target avenues. From perspective, underscores pivotal mitochondrial dysfunction sarcopenia, emphasizing elements oxidative overload, biogenesis, mitophagy, significance. At last, capture strides made treatment, ranging from nutritional exercise interventions pharmacological supplementation strategies. In sum, meticulously synthesizes latest scientific developments aiming enhance precision clinical practice insights refined innovative interventions, ultimately contributing optimized care field.

Language: Английский

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The Current Landscape of Pharmacotherapies for Sarcopenia

Drugs & Aging, Journal Year: 2024, Volume and Issue: 41(2), P. 83 - 112

Published: Feb. 1, 2024

Language: Английский

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The Inhibition of Autophagy and Pyroptosis by an Ethanol Extract of Nelumbo nucifera Leaf Contributes to the Amelioration of Dexamethasone-Induced Muscle Atrophy

Nutrients, Journal Year: 2023, Volume and Issue: 15(4), P. 804 - 804

Published: Feb. 4, 2023

Muscle atrophy is characterized by a decline in muscle mass and function. Excessive glucocorticoids the body due to aging or drug treatment can promote wasting. In this study, we investigated preventive effect of Nelumbo nucifera leaf (NNL) ethanolic extract on induced dexamethasone (DEX), synthetic glucocorticoid, mice its underlying mechanisms. The administration NNL increased weight, cross-sectional area, grip strength quadriceps (QD) gastrocnemius (GA) muscles DEX-induced mice. decreased expression atrophic factors, such as RING-finger protein-1 atrogin-1, autophagy Beclin-1, microtubule-associated protein 1A/1B-light chain 3 (LC3-I/II), sequestosome 1 (p62/SQSTM1) DEX-injected DEX injection levels NOD-like receptor pyrin domain-containing (NLRP3), cleaved-caspase-1, interleukin-1beta (IL-1β), cleaved-gasdermin D (GSDMD), which were significantly reduced (500 mg/kg/day). vitro studies using C2C12 myotubes also revealed that inhibited increase pyroptosis-related NF-κB. Overall, prevented downregulating ubiquitin–proteasome system, pathway, GSDMD-mediated pyroptosis are involved degradation.

Language: Английский

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Exploration and breakthrough in the mode of chondrocyte death - A potential new mechanism for osteoarthritis

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 170, P. 115990 - 115990

Published: Dec. 6, 2023

Osteoarthritis (OA) is a frequent chronic joint disease in orthopedics that effects individuals and society significantly. Obesity, aging, genetic susceptibility, misalignment are all known risk factors for OA, but its pathomechanism still poorly understood. Researches have revealed OA much complex process related to inflammation, metabolic chondrocyte death. It can affect parts of the characterized by causing death extracellular matrix descent. Previously, was thought develop from excessive mechanical loading leading destruction articular cartilage. Since some programmed cell deaths share pattern destruction, it likely also involves Even though apoptosis pyroptosis been investigated clarifing solely conventional pathways insufficient understand pathophysiology osteoarthritis. With more researches, has discovered osteoarthritis other new processes, including PANoptosis, ferroptosis, senescence, strongly associated. Among these, PANoptosis combines key traits pyroptosis, apoptosis, necrotic into highly coordinated dynamically balanced inflammatory mechanism. Furthermore, we think PANopotosis might obstruct necroptosis senescence. Therefore, order offer direction therapeutic treatment, evaluate development research on multiple chondrocytes OA.

Language: Английский

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Involvement of regulated cell deaths in aging and age-related pathologies

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 95, P. 102251 - 102251

Published: Feb. 28, 2024

Aging is a pathophysiological process that causes gradual and permanent reduction in all biological system functions. The phenomenon caused by the accumulation of endogenous exogenous damage as result several stressors, resulting significantly increased risks various age-related diseases such neurodegenerative diseases, cardiovascular metabolic musculoskeletal immune diseases. In addition, aging appears to be connected with mis-regulation programmed cell death (PCD), which required for regular turnover many tissues sustained division. According recent nomenclature, PCDs are physiological forms regulated (RCD) useful normal tissue development turnover. To some extent, types decrease RCD throughout aging, whereas others related an increase RCD. Perhaps widespread decline markers age due slowdown rate homeostatic adult tissues. As result, proper regulation requires careful balance pro-RCD anti-RCD components, may render signaling pathways more sensitive maladaptive signals during aging. Current research, on other hand, tries further dive into pathophysiology order develop therapies improve health longevity. this scenario, handling might helpful strategy human since it could reduce occurrence disorders, promoting healthy lifespan. review we propose general overview most mechanisms their connection promote targeted therapeutic strategies.

Language: Английский

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Association of vitamins B1 and B2 intake with early-onset sarcopenia in the general adult population of the US: a cross-sectional study of NHANES data from 2011 to 2018

Frontiers in Nutrition, Journal Year: 2024, Volume and Issue: 11

Published: March 8, 2024

Background Early-onset sarcopenia refers to the progressive loss of muscle mass and function that occurs at an early age. This condition perpetuates vicious cycle is associated with adverse outcomes. It important identify contributing factors for intervention prevention. While diet known impact mass, association B vitamins early-onset remains unexplored. Objectives To investigate intake risk in a cross-sectional study. Methods We conducted data analysis on total 8,711 participants aged between 20 59 years who took part National Health Nutrition Examination Survey (NHANES) from 2011 2018. was defined as SMI measured by DXA one standard deviation below sex-specific mean reference population. (B1, B2, B3, B6, B9, B12) assessed 24-h dietary recall. used weighted multiple logistic regression RCS models estimate OR 95% CI intake, adjusting demographic, physical, lifestyle, comorbidities, nutritional covariates. Results Higher vitamin B1 22% lower (OR = 0.78, 0.63–0.97, p 0.022), higher B2 16% 0.84, 0.74–0.97, 0.012) both genders. Gender-specific analyses showed 28% reduction among males each additional mg 0.72, 0.52–0.97, 0.038), 26% decrease females 0.74, 0.57–0.96, 0.021). No significant differences were found males, or females. The model suggested nonlinear relationship ( P Overall 0.001, Nonlinear 0.033), plateau effect above 3 mg/d. Conclusion may sarcopenia, gender differences. suggests potential increasing these through supplements. Further research warranted elucidate mechanisms design targeted interventions.

Language: Английский

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Resistin as a Systemic Inflammation-Related Biomarker for Sarcopenia in Patients With Chronic Obstructive Pulmonary Disease

Frontiers in Nutrition, Journal Year: 2022, Volume and Issue: 9

Published: July 12, 2022

Sarcopenia is common in patients with chronic obstructive pulmonary disease (COPD) and mainly caused by systemic inflammation. Resistin acts as a proinflammatory cytokine involved the activation of multiple inflammatory signaling pathways. The aim this study was to determine relationship between resistin levels inflammation assess clinical value circulating for sarcopenia COPD.

Language: Английский

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Pyroptosis regulation by Salmonella effectors

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 23, 2024

The genus Salmonella contains the most common foodborne pathogens frequently isolated from food-producing animals and is responsible for zoonotic infections in humans animals. infection can cause intestinal damage, resulting inflammation disruption of homeostasis more severe cases lead to bacteremia. Pyroptosis, a proinflammatory form programmed cell death, involved many disease processes. Inflammasomes, pyroptosis, along with their respective signaling cascades, are instrumental preservation homeostasis. In recent years, in-depth study our comprehension virulence factors effector proteins has reached an extensive level, deficit persists knowledge regarding intrinsic pathogenic mechanisms about necessitating continued pursuit understanding investigation. this review, we discuss occurrence pyroptosis induced by effectors provide new ideas elucidating regulatory through which trigger could pave way novel concepts strategies clinical prevention treatment associated diseases.

Language: Английский

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Cuproptosis and its potential role in musculoskeletal disease

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: April 11, 2025

Cuproptosis, a recently identified form of copper-dependent cell death, arises from intracellular copper dyshomeostasis. As an essential trace element, plays critical role in bioenergetic metabolism, redox regulation, and synaptic transmission. However, excessive exerts cytotoxic effects through multiple pathways, including increased reactive oxygen species (ROS) production, apoptotic cascade activation, necrotic membrane rupture, inflammatory responses, mitochondrial dysfunction. Distinct other death mechanisms, cuproptosis is characterized by ion binding to acetylated respiratory chain proteins, leading pathogenic protein aggregation, iron-sulfur cluster depletion, cellular collapse. Emerging evidence underscores aberrant accumulation resultant proteotoxic stress as pivotal contributors the pathogenesis musculoskeletal pathologies, osteoporosis, osteoarthritis, sarcopenia, osteosarcoma, intervertebral disc degeneration, spinal cord injury, biofilm-associated orthopedic infections. Understanding spatiotemporal regulation may provide novel opportunities for advancing diagnostic therapeutic approaches medicine. This review synthesizes current insights into molecular mechanisms cuproptosis, its diseases, potential biomarker-driven interventions.

Language: Английский

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Intelligent Predictive Risk Assessment and Management of Sarcopenia in Chronic Disease Patients Using Machine Learning and a Web-Based Tool

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 15, 2025

Background: Individuals with chronic diseases are at higher risk of sarcopenia, and precise prediction is essential for its prevention. This study aims to develop a scoring model using longitudinal data predict the probability sarcopenia in this population over next 3 5 years, thereby enabling early warning intervention. Methods: Using from nationwide survey initiated 2011, we selected patient records wave 1 (2011–2012) follow-up (2015–2016) as cohort. Retrospective collection included demographic information, health conditions, biochemical markers. After excluding missing values, total 2,891 adults conditions were enrolled. Sarcopenia was assessed based on Asian Working Group (AWGS) 2019 guidelines. A generalized linear mixed (GLMM) random effects diverse machine learning models utilized explore feature contributions risk. The Recursive Feature Elimination (RFE) algorithm employed optimize full Multilayer Perceptron (MLP) an online application tool. Results: Among population, 580 (20.1%) individuals diagnosed (2011-2012), 638 (22.1%) (2015-2016), while 2,165 (74.9%) not across period. MLP model, performed better than other three classic models, demonstrated ROC AUC 0.912, PR 0.401, sensitivity 0.875, specificity 0.844, Kappa value 0.376, F1 score 0.44. According SHapley Additive exPlanations (SHAP) scoring, weight, age, BMI, height, cholesterol, PEF, gender identified most important features disease individualsfor sarcopenia. Using RFE algorithm, six key variables—weight, gender—achieving about 0.9 Conclusion: We developed that incorporates only easily accessible variables, diseases. Additionally, created practical tool assist decision-making streamline clinical assessments.

Language: Английский

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