Buck Institute for Research on Aging, Novato, CA, USA.
Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Republic of Korea.
Nat Metab. 2022 Aug;4(8):995-1006. doi: 10.1038/s42255-022-00609-6. Epub 2022 Jul 28.
Ageing is the largest risk factor for many chronic diseases. Studies of heterochronic parabiosis, substantiated by blood exchange and old plasma dilution, show that old-age-related factors are systemically propagated and have pro-geronic effects in young mice. However, the underlying mechanisms how bloodborne factors promote ageing remain largely unknown. Here, using heterochronic blood exchange in male mice, we show that aged mouse blood induces cell and tissue senescence in young animals after one single exchange. This induction of senescence is abrogated if old animals are treated with senolytic drugs before blood exchange, therefore attenuating the pro-geronic influence of old blood on young mice. Hence, cellular senescence is neither simply a response to stress and damage that increases with age, nor a chronological cell-intrinsic phenomenon. Instead, senescence quickly and robustly spreads to young mice from old blood. Clearing senescence cells that accumulate with age rejuvenates old circulating blood and improves the health of multiple tissues.
衰老是许多慢性疾病的最大风险因素。通过异体共生的血液交换和老年血浆稀释研究证实，与衰老相关的因素在系统中传播，并对年轻小鼠具有促衰老作用。然而，血液传播因素如何促进衰老的潜在机制在很大程度上仍然未知。在这里，我们使用雄性小鼠的异体共生血液交换，发现单次血液交换后，老年小鼠的血液会诱导年轻动物的细胞和组织衰老。如果在血液交换前用衰老细胞清除药物治疗老年动物，则这种衰老的诱导作用会被消除，从而减弱老年血液对年轻小鼠的促衰老影响。因此，细胞衰老既不是随着年龄增长而增加的对压力和损伤的简单反应，也不是一种内在的细胞衰老现象。相反，衰老会迅速而强烈地从老年血液传播到年轻小鼠。清除随着年龄增长而积累的衰老细胞可以使老年循环血液恢复活力，并改善多种组织的健康状况。
