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Abstract：
Sarcopenia, a complex and debilitating condition characterized by progressive deterioration of skeletal muscle, is the primary cause of age-associated disability and significantly impacts healthspan in elderly patients. Despite its prevalence among the aging population, the underlying molecular mechanisms are still under investigation. The NLRP3 inflammasome is crucial in the innate immune response and has a significant impact on diseases related to inflammation and aging. Here, we investigated the expression of the NLRP3 inflammasome pathway and pro-inflammatory cytokines in skeletal muscle and peripheral blood of dependent and independent patients who underwent hip surgery. Patients were categorized into independent and dependent individuals based on their Barthel Index. The expression of NLRP3 inflammasome components was significantly upregulated in sarcopenic muscle from dependent patients, accompanied by higher levels of Caspase-1, IL-1β and IL-6. Among older dependent individuals with sarcopenia, there was a significant increase in the MYH3/MYH2 ratio, indicating a transcriptional shift in expression from mature to developmental myosin isoforms. Creatine kinase levels and senescence markers were also higher in dependent patients, altogether resembling dystrophic diseases and indicating muscle degeneration. In summary, we present evidence for the involvement of the NLRP3/ASC/NEK7/Caspase-1 inflammasome pathway with activation of pro-inflammatory SASP in the outcome of sarcopenia in the elderly.
摘要：
肌肉减少症,一种复杂和衰弱的状况，其特征是骨骼肌的进行性恶化，是与年龄相关的残疾的主要原因，并且显着影响老年患者的健康状况。尽管它在人口老龄化中普遍存在，潜在的分子机制仍在研究中。NLRP3炎性体在先天免疫应答中至关重要,并且对与炎症和衰老相关的疾病具有显著影响。这里,我们调查了NLRP3炎性小体通路和促炎细胞因子在接受髋部手术的依赖和独立患者骨骼肌和外周血中的表达.根据Barthel指数将患者分为独立和依赖个体。NLRP3炎性体成分在依赖患者的肌肉减少肌中表达显著上调，伴随着更高水平的Caspase-1、IL-1β和IL-6。在患有肌少症的老年依赖者中，MYH3/MYH2比率显着增加，表明表达从成熟到发育肌球蛋白亚型的转录转移。依赖患者的肌酸激酶水平和衰老标志物也较高，完全类似于营养不良疾病，表明肌肉退化。总之,我们提供了NLRP3/ASC/NEK7/Caspase-1炎症小体通路与促炎SASP激活在老年人肌肉减少症结局中的相关证据.
