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Open research questions in Muscle Physiology and Disorders

136 unresolved questions extracted from the limitations and future-work sections of 457 Muscle Physiology and Disorders papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • The complexity of the molecular systems required to maintain normal skeletal muscle function. The genetic and clinical heterogeneity of skeletal muscle disorders associated with abnormal excitation-contraction coupling. The need for a functional perspective that complements conventional genetic and clinicopathological classifications of ECC-related skeletal muscle disorders.

    Molecular genetics of skeletal muscle diseases associated with abnormal excitation–contraction coupling · 2026 · DOI

  • The complexity of the molecular systems required to maintain normal skeletal muscle function is not fully understood. The relationship between genetic and clinical heterogeneity and the underlying abnormalities in intracellular Ca²⁺ handling is not well characterized.

    Molecular genetics of skeletal muscle diseases associated with abnormal excitation–contraction coupling · 2026 · DOI

  • The complexity of the molecular mechanisms involved in myostatin signalling and muscle growth. The heterogeneity of methods used to diagnose and monitor sarcopenia. The need for careful regulation of pharmacological therapies due to potential adverse effects.

    Sarcopenia and Skeletal Muscle Dysfunction in Liver Cirrhosis: Clinical Perspectives of Myostatin Inhibition · 2026 · DOI

  • FSHD is a heterogeneous disorder, making it challenging to identify reliable biomarkers. The disease progresses slowly, making it difficult to capture subtle disease shifts. Muscle biopsies are no longer ethically justifiable, highlighting the need for circulating biomarkers.

    Sphingolipid Remodeling and Extracellular Vesicle Signatures Reflect Disease Severity in Facioscapulohumeral Dystrophy Driven by Mitochondrial Dysfunction and Endoplasmic Reticulum Stress · 2026 · DOI

  • Identifying robust biomarkers, particularly those reflecting metabolic dysregulation and oxidative stress, - Investigating the expression of selected genes involved in sphingolipid metabolism, - Validating the findings in a larger cohort, - Exploring the potential of circulating sphingolipids as therapeutic targets

    Sphingolipid Remodeling and Extracellular Vesicle Signatures Reflect Disease Severity in Facioscapulohumeral Dystrophy Driven by Mitochondrial Dysfunction and Endoplasmic Reticulum Stress · 2026 · DOI

  • further studies are needed to evaluate the effects of NooQ5 in other cell types, - further studies are needed to evaluate the effects of different concentrations of H2O2, - further studies are needed to evaluate the effects of different concentrations of BaCl2, - further studies are needed to evaluate the long-term effects of NooQ5

    NooQ5 Supplementation Promotes Myogenic Differentiation in C2C12 Cells Under Chemical and Oxidative Stress Models · 2026 · DOI

  • Investigating the relationship between oxidative stress and neurodegenerative diseases, - Examining the role of mitochondrial dynamics in sarcopenia and atrophy, - Studying the potential of therapeutic approaches for sarcopenia, such as exogenous antioxidants and carnitine supplementation

    Oxidative Stress in Neurodegenerative Disorders: A Key Driver in Impairing Skeletal Muscle Health · 2025 · DOI

  • The relationship between oxidative stress and neurodegenerative diseases is not fully understood, particularly in terms of muscle health. The underlying mechanisms of muscle degeneration in neurodegenerative diseases are not well understood. There is a need for therapeutic approaches that target the root causes of sarcopenia and atrophy.

    Oxidative Stress in Neurodegenerative Disorders: A Key Driver in Impairing Skeletal Muscle Health · 2025 · DOI

  • Methodological differences and age disparities may explain discrepancies in studies, - The study by Karlsen et al. had a limited sample size, - The mechanisms governing the potential removal of myonuclei remain speculative

    Skeletal muscle memory: implications for sports, aging and nutrition · 2025 · DOI

  • Investigating the mechanisms governing the potential removal of myonuclei, - Examining the role of epigenetic mechanisms in muscle memory, - Studying the effects of nutritional strategies on satellite cell responses and myonuclear accretion

    Skeletal muscle memory: implications for sports, aging and nutrition · 2025 · DOI

  • However, it remains unknown whether REDD1 exerts myofiber type-specific effects and through which precise mechanisms it regulates protein synthesis.

    REDD1 Regulates MERCS, Protein Synthesis and NMJ Stability in Fast Myofibers During Dexamethasone-Induced Muscle Wasting · 2026 · DOI

  • Limb muscles form through progressive splitting of the dorsal and ventral muscle masses, but the three-dimensional relationships between muscle splitting and surrounding tissues remain incompletely understood.

    Three-dimensional imaging reveals distinct muscle-vessel-nerve relationships during dorsal and ventral muscle splitting in the chicken forelimb · 2026 · DOI

  • Although immune and inflammatory mechanisms may contribute to disease variability, the prevalence and clinical impact of autoimmune diseases in FSHD remain unclear.

    Autoimmune Comorbidities as Modifiers of Phenotypic Heterogeneity in Facioscapulohumeral Dystrophy · 2026 · DOI

  • Dietary nucleotides offer metabolic and antioxidant benefits, yet their direct impact on skeletal myogenesis and structural recovery remains to be fully elucidated.

    NooQ5 Supplementation Promotes Myogenic Differentiation in C2C12 Cells Under Chemical and Oxidative Stress Models · 2026 · DOI

  • Limited data on outcomes in early‐diagnosed individuals have limited the understanding of the clinical impact of early diagnosis.

    Siblings With Duchenne Muscular Dystrophy: Exploring Diagnosis Age and Disease Progression in a Genetic Therapy‐Naïve Cohort · 2026 · DOI

  • While mitochondrial remodeling and function is essential for supporting the metabolic demands of myogenesis, the extent to which these processes are altered in aged satellite cells across cell states remains unclear.

    Altered senescence and mitochondrial transcriptome defines age-related changes in satellite cells · 2026 · DOI

  • Background Sarcopenia lacks sensitive molecular markers for early detection, and its relationship with integrated inflammatory cell-death programs remains unclear.

    Integrative transcriptomic and experimental analyses prioritize TPT1 as a PANoptosis-associated candidate molecular marker in sarcopenia · 2026 · DOI

  • While muscular dystrophies are often the primary therapeutic target for these cells, an underexplored application is their use in treating traumatic muscle injuries.

    Multitasking muscle: engineering iPSC-derived myogenic progenitors to do more · 2025 · DOI

  • While the transition from embryonic to mature fiber types is known to occur during late gestation, the precise temporal dynamics and molecular mechanisms underlying this process in sheep remain poorly understood.

    Decoding the prenatal clock of sheep muscle fiber type differentiation: a temporal map from embryonic to mature types · 2025 · DOI

  • Although the role of TGFβ1 in the regulation of ECM protein synthesis is well established, its involvement in the regulation of enzymes, such as MMPs, is still not well understood.

    Differential regulation of MMP activity by TGFβ1 in fast- and slow- twitch muscle repair: insights from EDL and soleus muscle-derived myoblasts · 2025 · DOI

  • However, the role of baicalin in the conversion of skeletal muscle fiber types and its underlying mechanisms remain unclear.

    Baicalin Promotes Skeletal Muscle Fiber Remodeling by Activating the p38MAPK/PGC-1α Signaling Pathway · 2025 · DOI

  • These findings suggest, for the first time, that FER and DFER may prevent obesity-related complications, including muscle atrophy and insulin resistance, thereby warranting further research into their long-term efficacy and safety.

    Feruloylacetone and Its Analog Demethoxyferuloylacetone Mitigate Obesity-Related Muscle Atrophy and Insulin Resistance in Mice · 2025 · DOI

  • How macrophages spatially adapt and diversify their functions to support the architectural requirements of actively regenerating tissue remains unknown.

    Spatiotemporal transcriptomic mapping of regenerative inflammation in skeletal muscle reveals a dynamic multilayered tissue architecture 3576 · 2025 · DOI

  • However, the protein-coding genes controlling this process remain incompletely understood.

    CLIC5 promotes myoblast differentiation and skeletal muscle regeneration via the BGN-mediated canonical Wnt/β-catenin signaling pathway · 2024 · DOI

  • Background: Although caffeine generally offers benefits to human health, its impact on bone metabolism remains unclear.

    Caffeine regulates both osteoclast and osteoblast differentiation via the AKT, NF-κB, and MAPK pathways · 2024 · DOI

Most-cited papers in Muscle Physiology and Disorders

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136 open questions have been extracted from the limitations and future-work passages of 457 Muscle Physiology and Disorders papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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