Unraveling the causes of sarcopenia: Roles of neuromuscular junction impairment and mitochondrial dysfunction

Physiological Reports, Journal Year: 2024, Volume and Issue: 12(1)

Published: Jan. 1, 2024

Abstract Sarcopenia is a systemic skeletal muscle disease characterized by decline in mass and function. Originally defined as an age‐associated condition, sarcopenia presently also encompasses muscular atrophy due to various pathological factors, such intensive care unit‐acquired weakness, inactivity, malnutrition. The exact pathogenesis of still unknown; herein, we review the roles neuromuscular junction mitochondria this condition. caused complex interdependent pathophysiological mechanisms, including aging, impairment, mitochondrial dysfunction, insulin resistance, lipotoxicity, endocrine oxidative stress, inflammation. Among these, instability dysfunction are particularly significant. Dysfunction can lead weakness or paralysis. Mitochondria, which plentiful neurons fibers, play important role transmission. Therefore, impairments both may be one key mechanisms leading sarcopenia. Moreover, article explores structural functional alterations sarcopenia, suggesting that deeper understanding these changes could provide valuable insights for prevention treatment

Language: Английский

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Fibro-adipogenic progenitors in physiological adipogenesis and intermuscular adipose tissue remodeling

Molecular Aspects of Medicine, Journal Year: 2024, Volume and Issue: 97, P. 101277 - 101277

Published: May 24, 2024

Excessive accumulation of intermuscular adipose tissue (IMAT) is a common pathological feature in various metabolic and health conditions can cause muscle atrophy, reduced function, inflammation, insulin resistance, cardiovascular issues, unhealthy aging. Although IMAT results from fat muscle, the mechanisms underlying its onset, development, cellular components, functions remain unclear. levels are influenced by several factors, such as changes environment, type origin, extent duration trauma, persistent activation fibro-adipogenic progenitors (FAPs). FAPs diverse transcriptionally heterogeneous population stromal cells essential for maintenance, neuromuscular stability, regeneration. However, cases chronic inflammation conditions, expand differentiate into adipocytes, resulting development abnormal ectopic IMAT. This review discusses role adipogenesis how they remodel It highlights evidence supporting FAP-derived adipocytes constituents IMAT, emphasizing their significance maintenance well involvement disorders, pathologies diseases. We also investigated intricate molecular pathways cell interactions governing FAP behavior, adipogenesis, diseases deconditioning. Finally, we hypothesize that impaired flexibility dysfunctional muscles impacts FAPs, leading to A deeper understanding biology regulating behavior fate new therapeutic strategies debilitating conditions.

Language: Английский

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Exercise and survival benefit in cancer patients: evidence from a comprehensive meta-analysis

GeroScience, Journal Year: 2025, Volume and Issue: unknown

Published: April 12, 2025

Language: Английский

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Explainable machine learning model for predicting skeletal muscle loss during surgery and adjuvant chemotherapy in ovarian cancer

Journal of Cachexia Sarcopenia and Muscle, Journal Year: 2023, Volume and Issue: 14(5), P. 2044 - 2053

Published: July 12, 2023

Skeletal muscle loss during treatment is associated with poor survival outcomes in patients ovarian cancer. Although changes mass can be assessed on computed tomography (CT) scans, this labour-intensive process impair its utility clinical practice. This study aimed to develop a machine learning (ML) model predict based data and interpret the ML by applying SHapley Additive exPlanations (SHAP) method.

Language: Английский

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Restoring Skeletal Muscle Health through Exercise in Breast Cancer Patients and after Receiving Chemotherapy

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(14), P. 7533 - 7533

Published: July 9, 2024

Breast cancer (BC) stands out as the most commonly type of diagnosed in women worldwide, and chemotherapy, a key component treatment, exacerbates cancer-induced skeletal muscle wasting, contributing to adverse health outcomes. Notably, impact chemotherapy on seems surpass that itself, with inflammation identified common trigger for wasting both contexts. In muscle, pro-inflammatory cytokines modulate pathways crucial delicate balance between protein synthesis breakdown, well satellite cell activation myonuclear accretion. Physical exercise consistently emerges therapeutic strategy counteract chemotherapy-induced ultimately enhancing patients’ quality life. However, “one size fits all” approach does not apply prescription BC patients, factors such age, menopause comorbidities influencing response exercise. Hence, tailored regimens, considering duration, frequency, intensity, type, are essential maximize efficacy mitigating improving disease Despite well-established anti-inflammatory role aerobic exercise, resistance proves equally or more beneficial terms mass strength gain, This review comprehensively explores molecular affected by distinct regimens patients during providing critical insights precise implementation prevent wasting.

Language: Английский

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Resistance and endurance exercise training improves muscle mass and the inflammatory/fibrotic transcriptome in a rhabdomyosarcoma model

Journal of Cachexia Sarcopenia and Muscle, Journal Year: 2023, Volume and Issue: 14(2), P. 781 - 793

Published: Feb. 16, 2023

Rhabdomyosarcoma (RMS) is an aggressive soft tissue sarcoma that most often develops in children. Chemoradiation therapy a standard treatment modality; however, the detrimental long-term skeletal muscle consequences of this juvenile cancer survivors include atrophy and fibrosis resulting decreased physical performance. Using novel model murine resistance endurance exercise training, we investigate its role preventing effects RMS plus therapy.Four-week-old male (n = 10) female C57Bl/6J mice were injected with M3-9-M cell into left gastrocnemius right limb serving as internal control (CON). Mice received systemic vincristine injection then five doses 4.8 Gy gamma radiation localized to hindlimb (RMS + Tx). randomly divided either sedentary (SED) or training (RET) groups. Changes performance, body composition, myocellular adaptations inflammatory/fibrotic transcriptome assessed.RET improved performance (P < 0.0001) composition 0.0004) compared SED. Tx resulted significantly lower weight 0.015) smaller myofibre cross-sectional area (CSA) 0.014). Conversely, RET higher 0.030) larger Type IIA 0.014) IIB fibre CSA. more 0.028), which was not prevented by RET. fewer mononuclear cells 0.05) satellite (stem) (MuSCs) immune than CON. fibro-adipogenic progenitors 0.05), trend for MuSCs 0.076) SED endothelial specifically limb. Transcriptomic changes revealed expression inflammatory fibrotic genes Tx, In model, also altered involved extracellular matrix turnover.Our study suggests preserves mass survivorship while partially restoring cellular dynamics transcriptome.

Language: Английский

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Myocellular adaptations to short‐term weighted wheel‐running exercise are largely conserved during C26‐tumour induction in male and female mice

Experimental Physiology, Journal Year: 2025, Volume and Issue: unknown

Published: April 24, 2025

Abstract This study investigated whether performing a translatable murine model of concurrent training after tumour induction affects adaptations in juvenile male and female tumour‐bearing mice. Male Balb/c mice were injected bilaterally with colon‐26 adenocarcinoma (C26) cells or PBS at 8 weeks age. Half the then performed 24 days voluntary wheel running progressively increased load (PoWeR training), whereas rest remained sedentary. Deuterium oxide‐based protein synthesis, muscle fibre‐type composition size, turnover mitochondrial markers assessed 25 induction. Average gastrocnemius fibre size was smaller PoWeR regardless males females, concomitant pronounced faster‐to‐slower transition. In mice, resulted greater Redd1 , Murf1 Pgc1α mRNA content than all other groups, along lower overall volume, food consumption synthesis relative to control animals. Molecular measures followed similar pattern PoWeR, but consumption, volume maintained. lowered gonadal fat during cancer cachexia both sexes, heart weight observed presence. A negative correlation found between distance. Collectively, has effect on cellular phenotype sexes presence, present despite molecular dysregulation.

Language: Английский

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Radiation induces long‐term muscle fibrosis and promotes a fibrotic phenotype in fibro‐adipogenic progenitors

Journal of Cachexia Sarcopenia and Muscle, Journal Year: 2023, Volume and Issue: 14(5), P. 2335 - 2349

Published: Sept. 6, 2023

Radiation-induced muscle pathology, characterized by atrophy and fibrotic tissue accumulation, is the most common debilitating late effect of therapeutic radiation exposure particularly in juvenile cancer survivors. In healthy muscle, fibro/adipogenic progenitors (FAPs) are required for maintenance regeneration, while pathology FAPs precursors exacerbated extracellular matrix deposition. However, role radiation-induced has not previously been explored.Four-week-old Male CBA or C57Bl/6J mice received a single dose (16 Gy) irradiation (IR) to hindlimb with shielded contralateral limb (CLTR) serving as non-IR control. Mice were sacrificed 3, 7, 14 (acute IR response), 56 days post-IR (long-term response). Changes skeletal morphology, myofibre composition, niche cellular dynamics, DNA damage, proliferation, mitochondrial respiration, metabolism changes progenitor cell fate where assessed.Juvenile resulted smaller cross-sectional area, type I IIA myofibres (P < 0.05) reduced proportion 0.05). Skeletal fibrosis was evident at post-IR. The IR-limb had fewer endothelial cells fibro-adipogenic Fewer satellite (stem) detected 3 induced FAP senescence 0.05), increased their fibrogenic differentiation 0.01), promoted glycolytic metabolism. Further, altered secretome manner that impaired fusion 0.05).Our study suggests following exposure, contribute long-term fibrosis. These findings provide rationale investigating FAP-targeted therapies ameliorate negative effects muscle.

Language: Английский

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Contemporary preclinical mouse models for pediatric rhabdomyosarcoma: from bedside to bench to bedside

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Feb. 2, 2024

Background Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue malignancy, characterized by high clinicalopathological and molecular heterogeneity. Preclinical in vivo models are essential for advancing our understanding of RMS oncobiology developing novel treatment strategies. However, diversity scholarly data on preclinical studies may challenge scientists clinicians. Hence, we performed a systematic literature survey contemporary mouse to characterize their phenotypes assess translational relevance. Methods We identified papers published between 01/07/2018 01/07/2023 searching PubMed Web Science databases. Results Out 713 records screened, 118 (26.9%) were included qualitative synthesis. Cell line-derived xenografts (CDX) commonly utilized (n = 75, 63.6%), followed patient-derived (PDX) syngeneic models, each accounting 11.9% 14), genetically engineered (GEMM) 7, 5.9%). Combinations different model categories reported 5.9% 7) studies. One study employed virus-induced model. Overall, 40.0% 30) utilizing CDX established alveolar (aRMS), while 38.7% 29) embryonal (eRMS). There 20.0% 15) that involved combination both aRMS eRMS subtypes. In one (1.3%), phenotype was spindle cell/sclerosing. Subcutaneous 66, 55.9%) more frequently used compared orthotopic 29, 24.6%). Notably, none cell lines derived from primary untreated tumors. Only minority investigated disseminated 16, 13.6%). The utilization areas testing drugs 64, 54.2%), studying tumorigenesis 56, 47.5%), tumor modeling 19, 16.1%), imaging 9, 7.6%), radiotherapy 6, 5.1%), long-term effects related 3, 2.5%), investigating biomarkers 1, 0.8%). no focused surgery. Conclusions This up-to-date review highlights need with dissemination Furthermore, efforts should be directed towards underexplored such as surgery, radiotherapy, biomarkers.

Language: Английский

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Voluntary wheel running mitigates disease in an Orai1 gain-of-function mouse model of tubular aggregate myopathy

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 29, 2023

Abstract Tubular aggregate myopathy (TAM) is an inherited skeletal muscle disease associated with progressive weakness, cramps, and myalgia. aggregates (TAs) are regular arrays of highly ordered densely packed SR straight-tubes in biopsies; the extensive presence TAs represent a key histopathological hallmark this TAM patients. caused by gain-of-function mutations proteins that coordinate store-operated Ca 2+ entry (SOCE): STIM1 sensor sarcoplasmic reticulum (SR) -permeable ORAI1 channels surface membrane. We have previously shown voluntary wheel running (VWR) prevents formation aging mice. Here, we assessed therapeutic potential endurance exercise (in form VWR) mitigating functional structural alterations knock-in mouse model ( Orai1 G100S/+ or GS mice) based on mutation pore. WT mice were singly-housed for six months (from two to eight age) either free-spinning locked low profile wheels. Six VWR significantly increased soleus peak tetanic specific force production, normalized FDB fiber store content, markedly reduced EDL from expression mitochondrial found be altered sedentary conjunction signature protein translation biosynthetic processes. Parallel proteomic analyses muscles revealed changes tight network pathways involved supramolecular complexes, which also following VWR. In summary, sustained improved slow twitch function, fast muscle, proteome consistent protective adaptions proteostasis, structure/function, complexes.

Language: Английский

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