Biology subjects

Deprez, A.

Publications and source records attributed to Deprez, A..

2 recordsLinked to original sources

bioRxiv2024

Peripheral Skeletal Muscle Alterations in Adults Born Preterm: An Observational Comparative Study

Prematurity is associated with reduced exercise capacity, which relies on the integrity of the cardiovascular, pulmonary, and skeletal muscle systems. Our animal model mimicking prematurity-associated conditions showed altered muscle composition and atrophy in adulthood. This study aimed to compare muscle composition and strength in adults born preterm versus full-term controls. This observational cohort study recruited 55 adults born preterm, [≤]29 weeks of gestation and 53 full-term controls who underwent musculoskeletal ultrasound imaging to assess morphology of the rectus femoris at rest and during a maximal voluntary contraction. Maximal voluntary contraction of the hands and legs were measured by manual dynamometry. In adults born preterm, there was a reduction in muscle strength (handgrip: -4.8 kg, 95% CI -9.1, -0.6; knee extensor: -44.6 N/m, 95% CI -63.4, -25.8) and muscle area (-130 mm2, 95% CI -207, -53), which was more pronounced with a history of bronchopulmonary dysplasia. Muscle stiffness was increased in the preterm group (0.4 m/s, 95% CI 0.04, 0.7). Prematurity is associated with alterations in skeletal muscle composition, area, and function in adulthood. These findings highlight the necessity to implement preventive and/or curative approaches to improve muscle development and function following preterm birth to enhance overall health in this population. Whats known on This SubjectPreterm birth is associated with reduced exercise capacity. However, the impact of preterm birth on skeletal muscle, a critical player of exercise capacity, in adulthood remains unclear. What This Study AddsOur findings provide novel insights into the potential long-term effects of preterm birth and the contributions of bronchopulmonary dysplasia on peripheral muscle-related health outcomes, such as muscle composition (reduced muscle area and increased muscle stiffness) and function (reduced muscle strength).

physiology↗

bioRxiv2022

Clearance of defective muscle stem cells by senolytics reduces the expression of senescence-associated secretory phenotype and restores myogenesis in myotonic dystrophy type 1.

Muscle weakness and atrophy are clinical hallmarks of myotonic dystrophy type 1 (DM1). Muscle stem cells, which contribute to skeletal muscle growth and repair, are also affected in this disease. However, the molecular mechanisms leading to this defective activity and the impact on the disease severity are still elusive. Here, we explored through an unbiased approach the molecular signature leading to myogenic cell defects in DM1. Single cell RNAseq data revealed the presence of a specific subset of DM1 myogenic cells expressing a senescence signature, characterized by the high expression of genes related to senescence-associated secretory phenotype (SASP). This profile was confirmed using different senescence markers in vitro and in situ. Accumulation of intranuclear RNA foci in senescent cells, suggest that RNA-mediated toxicity contribute to senescence induction. High expression of IL-6, a prominent SASP cytokine, in the serum of DM1 patients was identified as a biomarker correlating with muscle weakness and functional capacity limitations. Drug screening revealed that the BCL-XL inhibitor (A1155463), a senolytic drug, can specifically target senescent DM1 myoblasts to induce their apoptosis and reduce their SASP. Removal of senescent cells re-established the myogenic function of the non-senescent DM1 myoblasts, which displayed improved proliferation and differentiation capacity in vitro; and enhanced engraftment following transplantation in vivo. Altogether this study presents a well-defined senescent molecular signature in DM1 untangling part of the pathological mechanisms observed in the disease; additionally, we demonstrate the therapeutic potential of targeting these defective cells with senolytics to restore myogenesis.

cell biology↗