Abstract：
Senescent cells contribute to tissue aging and underlie the pathology of chronic diseases. The benefits of eliminating senescent cells have been demonstrated in several disease models, and the efficacy of senolytic drugs is currently being tested in humans. Exercise training has been shown to reduce cellular senescence in several tissues; however, the mechanisms responsible remain unclear. We found that myocyte-derived factors significantly extended the replicative lifespan of fibroblasts, suggesting that myokines mediate the anti-senescence effects of exercise. A number of proteins within myocyte-derived factors were identified by mass spectrometry. Among these, pigment epithelium-derived factor (PEDF) exerted inhibitory effects on cellular senescence. Eight weeks of voluntary running increased Pedf levels in skeletal muscles and suppressed senescence markers in the lungs. The administration of PEDF reduced senescence markers in multiple tissues and attenuated the decline in respiratory function in the pulmonary emphysema mouse model. We also showed that blood levels of PEDF inversely correlated with the severity of COPD in patients. Collectively, these results strongly suggest that PEDF contributes to the beneficial effects of exercise, potentially suppressing cellular senescence and its associated pathologies.
摘要：
衰老细胞有助于组织衰老并成为慢性疾病病理的基础。已经在几种疾病模型中证明了消除衰老细胞的益处，目前正在人体中测试抗衰老药物的功效。运动训练已被证明可以减少几种组织的细胞衰老；然而，负责的机制仍不清楚。我们发现肌细胞衍生因子可显着延长成纤维细胞的复制寿命，提示肌力因子介导运动的抗衰老作用。通过质谱鉴定了肌细胞衍生因子内的许多蛋白质。其中,色素上皮衍生因子（PEDF）对细胞衰老具有抑制作用。八周的自愿跑步增加了骨骼肌中的Pedf水平，并抑制了肺部的衰老标志物。在肺气肿小鼠模型中，PEDF的给药减少了多种组织中的衰老标志物，并减轻了呼吸功能的下降。我们还表明，血液中PEDF的水平与COPD患者的严重程度呈负相关。总的来说，这些结果强烈表明PEDF有助于运动的有益效果，潜在抑制细胞衰老及其相关病理。
