小柯机器人

表达p16^high的衰老细胞对于小鼠健康是必不可少的，这一成果由法国国家健康与医学研究院Dmitry V. Bulavin团队取得。该研究于2020年6月1日在线发表于《细胞-代谢》杂志。

研究人员构建了两个p16^Ink4a敲入的小鼠模型，p16^Ink4a是衰老细胞的最佳标记。使用遗传谱系追踪方法，研究人员发现年龄诱发的p16^high衰老是一个缓慢的过程，大约在10至12个月大时出现。大多数p16^High细胞是血管内皮细胞，主要存在于肝窦（LSECs）中，其次是巨噬细胞和脂肪细胞。

反过来，连续或急性清除p16^High衰老细胞会破坏血液组织屏障，继而引起肝脏和血管周围组织纤维化，损害健康。该数据表明，衰老的LSEC在去除后不会被替换，在衰老个体中具有重要的结构和功能作用。反过来，延缓衰老或衰老LSEC的替换可能是减缓衰老的有效方法。

据悉，衰老细胞的积累可以诱发许多与年龄相关的表型和疾病。因此，人们认为去除衰老细胞可以延长寿命。

附：英文原文

Title: Defined p16High Senescent Cell Types Are Indispensable for Mouse Healthspan

Author: Laurent Grosse, Nicole Wagner, Alexander Emelyanov, Clement Molina, Sandra Lacas-Gervais, Kay-Dietrich Wagner, Dmitry V. Bulavin

Issue&Volume: 2020-06-01

Abstract: The accumulation of senescent cells can drive many age-associated phenotypes and pathologies.Consequently, it has been proposed that removing senescent cells might extend lifespan.Here, we generated two knockin mouse models targeting the best-characterized markerof senescence, p16Ink4a. Using a genetic lineage tracing approach, we found that age-induced p16High senescence is a slow process that manifests around 10–12 months of age. The majorityof p16High cells were vascular endothelial cells mostly in liver sinusoids (LSECs), and to lesserextent macrophages and adipocytes. In turn, continuous or acute elimination of p16High senescent cells disrupted blood-tissue barriers with subsequent liver and perivasculartissue fibrosis and health deterioration. Our data show that senescent LSECs are notreplaced after removal and have important structural and functional roles in the agingorganism. In turn, delaying senescence or replacement of senescent LSECs could representa powerful tool in slowing down aging.

DOI: 10.1016/j.cmet.2020.05.002

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30241-2

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