Age-related muscle mass and strength decline (sarcopenia) impairs the performance of daily living activities and can lead to mobility disability/limitation in older adults. Biological pathways in muscle that lead to mobility problems have not been fully elucidated. Immunoglobulin G (IgG) infiltration in muscle is a known marker of increased fiber membrane permeability and damage vulnerability, but whether this translates to impaired function is unknown. Here, we report that IgG1 and IgG4 are abundantly present in the skeletal muscle (vastus lateralis) of ~ 50% (11 out of 23) of older adults (> 65 years) examined. Skeletal muscle IgG1 was inversely correlated with physical performance (400 m walk time: r = 0.74, p = 0.005; SPPB score: r = − 0.73, p = 0.006) and muscle strength (r = − 0.6, p = 0.05). In a murine model, IgG was found to be higher in both muscle and blood of older, versus younger, C57BL/6 mice. Older mice with a higher level of muscle IgG had lower motor activity. IgG in mouse muscle co-localized with cardiac troponin T (cTnT) and markers of complement activation and apoptosis/necroptosis. Skeletal muscle–inducible cTnT knockin mice also showed elevated IgG in muscle and an accelerated muscle degeneration and motor activity decline with age. Most importantly, anti-cTnT autoantibodies were detected in the blood of cTnT knockin mice, old mice, and older humans. Our findings suggest a novel cTnT-mediated autoimmune response may be an indicator of sarcopenia.

与年龄相关的肌肉质量和力量下降（肌肉减少症）会损害日常生活活动的表现，并可能导致老年人行动不便/受限。肌肉中导致活动性问题的生物学途径尚未完全阐明。肌肉中的免疫球蛋白 G (IgG) 浸润是纤维膜通透性和损伤易损性增加的已知标志，但这是否转化为功能受损尚不清楚。在这里，我们报告说，IgG1 和 IgG4 大量存在于约 50%（23 人中的 11 人）所检查的老年人（> 65 岁）的骨骼肌（股外侧肌）中。骨骼肌 IgG1 与身体表现呈负相关（400 米步行时间：r  = 0.74，p  = 0.005；SPPB 评分：r  = − 0.73，p  = 0.006) 和肌肉力量 ( r  = − 0.6, p  = 0.05)。在小鼠模型中，发现 IgG 在老年 C57BL/6 小鼠的肌肉和血液中含量高于年轻 C57BL/6 小鼠。肌肉 IgG 水平较高的老年小鼠运动活动较低。小鼠肌肉中的 IgG 与心肌肌钙蛋白 T (cTnT) 以及补体激活和细胞凋亡/坏死性凋亡的标志物共定位。骨骼肌可诱导的 cTnT 敲入小鼠也显示肌肉中 IgG 升高，并且随着年龄的增长，肌肉退化和运动活动加速下降。最重要的是，在 cTnT 敲入小鼠、老年小鼠和老年人的血液中检测到抗 cTnT 自身抗体。我们的研究结果表明，一种新型的 cTnT 介导的自身免疫反应可能是肌肉减少症的一个指标。