Sex Differences in Inflammation and Muscle Wasting in Aging and Disease

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(5), P. 4651 - 4651

Published: Feb. 28, 2023

Only in recent years, thanks to a precision medicine-based approach, have treatments tailored the sex of each patient emerged clinical trials. In this regard, both striated muscle tissues present significant differences between two sexes, which may important consequences for diagnosis and therapy aging chronic illness. fact, preservation mass disease conditions correlates with survival; however, should be considered when protocols maintenance are designed. One obvious difference is that men more than women. Moreover, sexes differ inflammation parameters, particularly response infection disease. Therefore, unsurprisingly, women respond differently therapies. review, we an up-to-date overview on what known about skeletal physiology disfunction, such as disuse atrophy, age-related sarcopenia, cachexia. addition, summarize underly aforementioned because pro-inflammatory cytokines deeply affect homeostasis. The comparison these three their sex-related bases interesting different forms atrophy share common mechanisms; instance, those responsible protein dismantling similar although differing terms kinetics, severity, regulatory mechanisms. pre-clinical research, exploring sexual dimorphism could highlight new efficacious or recommend implementation existing one. Any protective factors discovered one exploited achieve lower morbidity, reduce severity disease, avoid mortality opposite sex. Thus, understanding sex-dependent responses pivotal importance design innovative, tailored, efficient interventions.

Language: Английский

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Sex differences in skeletal muscle revealed through fiber type, capillarity, and transcriptomics profiling in mice

Physiological Reports, Journal Year: 2021, Volume and Issue: 9(18)

Published: Sept. 1, 2021

Skeletal muscle anatomy and physiology are sexually dimorphic but molecular underpinnings muscle-specificity not well-established. Variances in metabolic health, fitness level, sedentary behavior, genetics, age make it difficult to discern inherent sex effects humans. Therefore, mice under well-controlled conditions were used determine female male (n = 19/sex) skeletal fiber type/size capillarity superficial deep gastrocnemius (GA-s, GA-d), soleus (SOL), extensor digitorum longus (EDL), plantaris (PLT), transcriptome patterns also determined (GA, SOL). Summed weight strongly correlated with lean body mass (r2 0.67, p < 0.0001, both sexes). Other phenotypes muscle-specific: e.g., (higher density, GA-s), myofiber size (higher, EDL), type lower I II prevalences, respectively, There broad differences transcriptomics, >6000 (GA) >4000 (SOL) mRNAs differentially-expressed by sex; only a minority of these shared across GA SOL. Pathway analyses revealed ribosome biology, transcription, RNA processing. Curation transcripts SOL, literature datasets from humans, identified 11 genes that we propose canonical innate muscle: Xist, Kdm6a, Grb10, Oas2, Rps4x females) Ddx3y, Kdm5d, Irx3, Wwp1, Aldh1a1, Cd24a males). These those the highest "sex-biased" expression our study do contain estrogen-response elements (exception, Greb1), subset proposed be regulated through androgen response elements. We hypothesize sexual dimorphism humans is triggered then maintained classic X inactivation (Xist, Y activation (Ddx3y, males), coincident engagement encoded (Kdm6a) (Kdm5d) demethylase epigenetic regulators complemented modulation at some regions genome respond androgen.

Language: Английский

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Sex differences in endurance exercise capacity and skeletal muscle lipid metabolism in mice

Physiological Reports, Journal Year: 2022, Volume and Issue: 10(3)

Published: Feb. 1, 2022

Previous studies suggest that sex differences in lipid metabolism exist with females demonstrating a higher utilization of lipids during exercise, which is mediated partly by increased muscle triglycerides. However, whether these changes contribute directly to endurance exercise performance unclear. Therefore, the objective this study was investigate contribution substrate capacity (EEC) mice. Male and female C57BL/6-NCrl mice were subjected an EEC test until exhaustion on motorized treadmill. The treadmill set at 10% incline, speed gradually from 10.2 m/min 22.2 fixed intervals for up 2.5 h. Tissues blood harvested immediately following EEC. A cohort sedentary, non-exercised male used as controls. Females outperformed males ~25% Serum levels both fatty acids ketone bodies ~50% end In sedentary mice, skeletal triglyceride content significantly greater compared males. Gene expression analysis demonstrated genes involved acid oxidation no associated glucose uptake or body oxidation. findings have ability mobilize utilize energy.

Language: Английский

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Fiber-type traps: revisiting common misconceptions about skeletal muscle fiber types with application to motor control, biomechanics, physiology, and biology

Journal of Applied Physiology, Journal Year: 2023, Volume and Issue: 136(1), P. 109 - 121

Published: Nov. 23, 2023

Skeletal muscle is a highly complex tissue that studied by scientists from wide spectrum of disciplines, including motor control, biomechanics, exercise science, physiology, cell biology, genetics, regenerative medicine, orthopedics, and engineering. Although this diversity in perspectives has led to many important discoveries, historically, there been limited overlap discussions across fields. This misconceptions oversimplifications about biology can create confusion potentially slow scientific progress The purpose synthesis paper bring together research multiple fields identify common assumptions related fiber type are points concern clarify. These include

Language: Английский

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Translatability of mouse muscle-aging for humans: the role of sex

GeroScience, Journal Year: 2024, Volume and Issue: 46(3), P. 3341 - 3360

Published: Jan. 24, 2024

Abstract Muscle-aging drives sarcopenia and is a major public health issue. Mice are frequently used as model for human muscle-aging, however, research investigating their translational value limited. In addition, mechanisms underlying muscle-aging may have sex-specific features in humans, but it not yet assessed whether these recapitulated mice. Here, we studied the effects of aging on functional, histological transcriptional level at multiple timepoints male female mice (4, 17, 21 25 months), with particular emphasis sex-differences. The natural transcriptome quadriceps muscle were compared to humans pathway level. Significant loss mass occurred late, months, both (-17%, quadriceps) (-10%, young control Concomitantly, found female, mice, slower movement speed aged groups (P < 0.001). Consistently, weighted gene co-expression network analysis revealed stronger association between aging-related reduction changes male, distinctive last age group (25 which highlights necessity careful selection using model. Furthermore, contrasting more (4090 vs. 2285 differentially expressed genes respectively). Subsequently, related pathways characteristic humans. conclusion, our data show that sex has critical effect mouse trajectory, although do necessarily reflect differences observed trajectory.

Language: Английский

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Key considerations for investigating and interpreting autophagy in skeletal muscle

Autophagy, Journal Year: 2024, Volume and Issue: 20(10), P. 2121 - 2132

Published: July 15, 2024

Skeletal muscle plays a crucial role in generating force to facilitate movement. is heterogenous tissue composed of diverse fibers with distinct contractile and metabolic profiles. The intricate classification skeletal exists on continuum ranging from type I (slow-twitch, oxidative) II (fast-twitch, glycolytic). distribution characteristics within between muscles profoundly influences cellular signaling; however, this has not been broadly discussed as it relates macroautophagy/autophagy. growing interest autophagy research underscores the necessity comprehending interplay autophagic responses among different properties, profiles, other related signaling processes. We recommend approaching interpretation findings careful consideration for two key reasons: 1) behaviors or various perturbations, 2) potential impact alterations fiber profile observed outcomes. This review provides an overview response muscles/fibers types Further, discusses conditions diseases that may differentially affect muscle. Finally, we provide points better enable researchers fine-tune design experiments.

Language: Английский

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Skeletal Muscle Microvascular Dysfunction in Obesity-Related Insulin Resistance: Pathophysiological Mechanisms and Therapeutic Perspectives

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(2), P. 847 - 847

Published: Jan. 13, 2022

Obesity is a worrisomely escalating public health problem globally and one of the leading causes morbidity mortality from noncommunicable disease. The epidemiological link between obesity broad spectrum cardiometabolic disorders has been well documented; however, underlying pathophysiological mechanisms are only partially understood, effective treatment options remain scarce. Given its critical role in glucose metabolism, skeletal muscle increasingly become focus attention understanding impaired insulin function associated metabolic sequelae. We examined current evidence on relationship microvascular dysfunction resistance obesity. A growing body suggest an intimate reciprocal glucometabolic physiology. phenotype characterized by structural functional changes microcirculation which contribute to disturbed homeostasis. Several interconnected etiologic molecular have suggested, including endothelial several factors, extracellular matrix remodelling, induction oxidative stress immunoinflammatory phenotype. further correlated currently available pharmacological agents that deductive therapeutic relevance explored mechanisms, highlighting potential clinical perspective treatment.

Language: Английский

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Skeletal muscle ribosome analysis: A comparison of common assay methods and utilization of a novel RiboAb antibody cocktail

Physiological Reports, Journal Year: 2025, Volume and Issue: 13(1)

Published: Jan. 1, 2025

Abstract While total RNA concentrations putatively represent ribosome content, there is a need to homologize various quantification approaches. Thus, ([RNA]) provided through UV–Vis spectroscopy (UV), fluorometry‐only (Fluor), and fluorometry‐based microfluidic chip electrophoresis (MFGE) were examined in C2C12 myotubes mouse skeletal muscle determine if values aligned with [18S + 28S rRNA] (i.e., criterion metric). A novel antibody cocktail (termed RiboAb ) was also tested compared these models. In myotubes, 24‐h IGF‐1 treatments increased (~2.0‐fold) [RNA] based on UV (~1.9‐fold), Fluor (~2.3 fold), MFGE (~2.1‐fold). C57BL/6 mice, 10 days of mechanical overload (MOV) elevated plantaris (~1.7‐fold) according (~1.5‐fold), (~1.6‐fold), (~1.8‐fold). Myotube levels significantly higher MOV, respectively, versus controls (1.3‐fold 1.7‐fold, respectively), correlated ( r = 0.637 0.853, p ≤ 0.005). UV, Fluor, are seemingly valid surrogates cell/tissue although each method has advantages (e.g., ease use) disadvantages magnitudes bias) discussed herein. Finally, the may this should be further explored other

Language: Английский

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An exploratory study of serum creatine kinase as a prognostic marker for patients with resectable pancreatic cancer: looking into the relationship with body composition

Nutrition Journal, Journal Year: 2025, Volume and Issue: 24(1)

Published: Feb. 1, 2025

Among cancer patients, pancreatic patients have the highest rate of sarcopenia, which is a critical prognostic factor. Serum creatine kinase (CK) closely related to skeletal muscle mass and has been reported decline with progression cancer. This study investigated whether preoperative serum CK associated survival Data were obtained from pathologically confirmed between June 2016 March 2022. The significance was analyzed based on sex-stratified groups. Kaplan-Meier method used compare overall (OS) disease-free (DFS). Multivariate Cox proportional hazards models determine factors. Body composition abdominal CT images explore sex-specific associations area (SMA) levels. A total 166 included in this study. Sarcopenia presented 70 (42.2%). low level showed significant correlation diagnosis sarcopenia male (P = 0.026). levels did not predict outcome female while notably linked shorter OS (median OS: 15 months vs. 33 months, P 0.011; median DFS: 5 14 0.007). analyses further effect predicting (CK>44 IU/L, HR:0.226, 95% CI:0.107-0.478, < 0.001) DFS HR:0.272, CI:0.139-0.529, patients. Correlation analysis revealed association SMA (r 0.225, 0.025), such observed 0.088, 0.478). pretherapeutic may represent simple marker for poor resectable cancer, thereby aiding selection therapeutic strategies.

Language: Английский

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Genetic and metabolic insights into sexual dimorphism in the flexor carpi radialis of Asiatic toads (Bufo gargarizans) associated with amplexus behavior

BMC Genomics, Journal Year: 2025, Volume and Issue: 26(1)

Published: Feb. 24, 2025

Sexual dimorphism, a widespread phenomenon across the animal kingdom, encompasses differences between sexes in size, morphology, and physiological traits. In this study, we investigated sexual dimorphism flexor carpi radialis (FCR) muscle, which is critical for amplexus Asiatic toads (Bufo gargarizans), using integrated transcriptomic metabolomic approaches. Male exhibited significantly larger FCR muscles, reflecting enhanced muscle function required sustained amplexus. Transcriptomic analysis identified 818 differentially expressed genes (DEGs) sexes, with 389 upregulated 429 downregulated males, predominantly associated contraction, sarcomere organization, energy metabolism. Metabolomic profiling revealed 69 metabolites (DEMs), male-biased enrichment pathways involved protein synthesis degradation, metabolism, material transport. Integrated pinpointed key metabolic pathways—such as glycine, serine, threonine metabolism; alanine, aspartate, glutamate fatty acid degradation; tricarboxylic (TCA) cycle—as central to observed dimorphism. Among these, AGXT, ACADL, ACAT1, MDH2, SUCLG2 emerged pivotal regulators. Collectively, these findings provide novel insights into genetic basis of B. gargarizans, offering deeper understanding evolutionary mechanisms driving sex-specific traits vertebrates.

Language: Английский

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