State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Institute for Stem cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Institute for Stem cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Cell. 2023 Jan 19;186(2):287-304.e26. doi: 10.1016/j.cell.2022.12.017. Epub 2023 Jan 6.
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.
是否以及如何某些具有病毒起源的转座元件，如内源性逆转录病毒（ERVs）在我们的基因组中处于休眠状态，可以被唤醒并有助于衰老过程，这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 ERVs，被解锁转录病毒基因并产生逆转录病毒样颗粒（RVLPs）。这些 HERVK RVLPs 构成了一种可传播的信息，可在年轻细胞中引发衰老表型，可被中和抗体阻断。ERV 的激活也在老年灵长类动物和小鼠的器官以及人类组织和老年血清中观察到。它们的抑制减轻了细胞衰老和组织退化，并在某种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。
