Resurrection of endogenous retroviruses during aging reinforces senescence
Resurrection of endogenous retroviruses during aging reinforces senescence
复制标题
衰老过程中内源性逆转录病毒的复活会加剧衰老
DOI：
10.1016/j.cell.2022.12.017
复制
发表时间：
2023-01-19
期刊：
影响因子：
64.5
通讯作者：
Liu，Guang-Hui
中科院分区：
文献类型：
--
作者：
Liu，Xiaoqian;Liu，Zunpeng;Liu，Guang-Hui
病毒起源的某些转座因子，如潜伏在我们基因组中的内源性逆转录病毒（erv），是否以及如何被唤醒并促进衰老过程，在很大程度上是未知的。在人类衰老细胞中，我们发现HERVK (HML-2)，最近整合的人类erv，被解锁转录病毒基因并产生逆转录病毒样颗粒（rvlp）。这些HERVK rvlp构成了一个可传递的信息，在年轻细胞中引发衰老表型，这可以被中和抗体阻断。在老年灵长类动物和小鼠的器官以及老年人的人体组织和血清中也观察到erv的活化。它们的抑制减轻了细胞衰老和组织退化，并在一定程度上减轻了机体衰老。这些发现表明，erv的复活是细胞衰老和组织衰老的标志和驱动力。
Whether and how certain transposable elements with viral origins, such as endogenous retroviruses (ERVs) dormant in our genomes, can become awakened and contribute to the aging process is largely unknown. In human senescent cells, we found that HERVK (HML-2), the most recently integrated human ERVs, are unlocked to transcribe viral genes and produce retrovirus-like particles (RVLPs). These HERVK RVLPs constitute a transmissible message to elicit senescence phenotypes in young cells, which can be blocked by neutralizing antibodies. The activation of ERVs was also observed in organs of aged primates and mice as well as in human tissues and serum from the elderly. Their repression alleviates cellular senescence and tissue degeneration and, to some extent, organismal aging. These findings indicate that the resurrection of ERVs is a hallmark and driving force of cellular senescence and tissue aging.