Liu Xiaoqian, Jiao Haifeng, Zhang Baohu, Zhang Sheng, Yan Kaowen, Qu Jing, Zhang Weiqi, Yu Li, Liu Guang-Hui
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, China.
Life Med. 2023 Dec 8;2(6):lnad050. doi: 10.1093/lifemedi/lnad050. eCollection 2023 Dec.
Aging is a complex and heterogeneous process, raising important questions about how aging is differently impacted by underlying genetics and external factors. Recently, migrasomes, newly discovered organelles, have been identified to play important roles in various physiological and pathological processes by facilitating cell-to-cell communication. Thus far, their involvement in cellular senescence and aging remains largely unexplored. In this study, we aimed to investigate how migrasomes impact on cellular aging by leveraging multiple cellular senescence models, including replicatively senescent (RS), pathologically senescent and stress-induced senescent human mesenchymal stem cells (hMSCs), as well as RS human primary fibroblasts. In all cellular aging models, we detected an enhanced formation of migrasomes. Notably, migrasomes in senescent cells exhibited an accumulation of numerous aging hallmarks, such as dysfunctional mitochondria, endogenous retroviruses, and senescence-associated pro-inflammatory cytokines. Furthermore, we discovered that migrasomes derived from senescent cells can be taken up by young cells, thereby transferring aging signals and subsequently causing premature senescence phenotypes in recipient cells. Mechanistically, we found that treatment with migrasomes derived from senescent cells activated the innate immune response. Thus, our study sheds light on a pivotal role of migrasomes in mediating the contagiousness of aging.
衰老过程复杂且具有异质性，这引发了关于潜在遗传学和外部因素如何对衰老产生不同影响的重要问题。最近，迁移体作为新发现的细胞器，已被证实通过促进细胞间通讯在各种生理和病理过程中发挥重要作用。到目前为止，它们在细胞衰老和老化中的作用仍 largely 未被探索。在本研究中，我们旨在利用多种细胞衰老模型，包括复制性衰老（RS）、病理性衰老和应激诱导衰老的人间充质干细胞（hMSCs）以及 RS 人原代成纤维细胞，来研究迁移体如何影响细胞衰老。在所有细胞衰老模型中，我们检测到迁移体的形成增强。值得注意的是，衰老细胞中的迁移体表现出大量衰老特征的积累，如线粒体功能障碍、内源性逆转录病毒和衰老相关的促炎细胞因子。此外，我们发现衰老细胞来源的迁移体可以被年轻细胞摄取，从而传递衰老信号并随后在受体细胞中导致过早衰老表型。从机制上讲，我们发现用衰老细胞来源的迁移体处理可激活先天免疫反应。因此，我们的研究揭示了迁移体在介导衰老传染性方面的关键作用。
