我们的研究是使用临床相关定义来表征C57BL/6J小鼠中的肌肉减少症,以研究潜在的分子机制。成年雄性(23-32月龄)和雌性(27-28月龄)C57BL/6J小鼠被分类为非,可能-,或基于对握力的评估而减少肌肉,肌肉质量,和跑步机运行时间,使用低于年轻同行平均值的2个SDs作为截止点。在23-26个月大的雄性小鼠中发现9%-22%的肌肉减少症患病率,与年龄相关的肌肉功能下降比质量更严重。与男性相比,年龄在27-28个月之间的女性显示出较少的肌少症,但可能的病例更多。随着肌少症的发展,在男性中观察到肌肉收缩性降低和IIB型纤维尺寸降低的趋势。线粒体生物发生,氧化能力,AMPK-自噬信号随着男性肌少症的发展而减少,与线粒体代谢相关的途径与肌肉质量呈正相关。在线粒体生物发生中没有观察到年龄或肌肉减少相关的变化,OXPHOS复合物,AMPK信号,线粒体自噬,或者女性的atrogenes。我们的结果突出了与年龄相关的肌肉质量和功能下降的不同轨迹,提供与肌肉减少症进展相关的性别依赖性分子变化的见解,这可能为新的治疗干预措施的未来发展提供信息。
Our study was to characterize sarcopenia in C57BL/6J mice using a clinically relevant definition to investigate the underlying molecular mechanisms. Aged male (23-32 months old) and female (27-28 months old) C57BL/6J mice were classified as non-, probable-, or sarcopenic based on assessments of grip strength, muscle mass, and treadmill running time, using 2 SDs below the mean of their young counterparts as cutoff points. A 9%-22% prevalence of sarcopenia was identified in 23-26 month-old male mice, with more severe age-related declines in muscle function than mass. Females aged 27-28 months showed fewer sarcopenic but more probable cases compared with the males. As sarcopenia progressed, a decrease in muscle contractility and a trend toward lower type IIB fiber size were observed in males. Mitochondrial biogenesis, oxidative capacity, and AMPK-autophagy signaling decreased as sarcopenia progressed in males, with pathways linked to mitochondrial metabolism positively correlated with muscle mass. No age- or sarcopenia-related changes were observed in mitochondrial biogenesis, OXPHOS complexes, AMPK signaling, mitophagy, or atrogenes in females. Our results highlight the different trajectories of age-related declines in muscle mass and function, providing insights into sex-dependent molecular changes associated with sarcopenia progression, which may inform the future development of novel therapeutic interventions.