Understanding the loss of kidney function resulting from kidney aging has become an emerging research focus that will facilitate the future development of antisenolytic treatments. In this issue of the JCI, Pippin et al. first identified PD-1 upregulation in the aged mouse podocyte via unbiased RNA-seq analysis. Overexpression of PD-1 in immortalized mouse podocytes induced cell death and a senescence-associated secretory phenotype, suggesting the pathological role of PD-1 upregulation in aged podocytes. Blocking PD-1 signaling via a neutralizing anti-PD-1 antibody reversed the aged phenotype in the aged mice and ameliorated proteinuria in an experimental focal segmental glomerulosclerosis (FSGS) mouse model. These findings highlight the role of PD-1 signaling in kidney aging and its therapeutic potential for human clinical trials.

中文翻译：

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老化肾小球：PD-1 和足细胞之间的联系


了解肾脏衰老导致的肾功能丧失已成为一个新兴的研究热点，这将有助于抗衰老治疗的未来发展。在本期JCI中，Pippin 等人。首先通过无偏 RNA-seq 分析确定了衰老小鼠足细胞中 PD-1 的上调。 PD-1 在永生化小鼠足细胞中的过度表达会诱导细胞死亡和衰老相关的分泌表型，这表明 PD-1 上调在衰老足细胞中的病理作用。通过中和性抗 PD-1 抗体阻断 PD-1 信号传导可逆转老年小鼠的衰老表型，并改善实验性局灶节段性肾小球硬化 (FSGS) 小鼠模型中的蛋白尿。这些发现强调了 PD-1 信号传导在肾脏衰老中的作用及其在人类临床试验中的治疗潜力。