小柯机器人

西班牙庞培法布拉大学Pura Muñoz-Cánoves等研究人员合作发现，衰老图谱揭示阻碍肌肉再生的老年性炎症微环境。2022年12月21日，国际知名学术期刊《自然》发表了这一成果。

研究人员发现，衰老细胞是骨骼肌再生微环境的组成部分，在生命的各个阶段都会抑制再生。通过结合单细胞转录组学和衰老细胞富集分选方案，研究人员克服了衰老细胞稀少的技术限制。研究人员从年轻和年老小鼠的受损肌肉中鉴定并分离出不同的衰老细胞类型。更深入的转录组、染色质和通路分析显示，在不同的细胞类型、再生时间和衰老过程中，细胞的身份特征以及两个普遍的衰老标志（炎症和纤维化）得到了保护。衰老的细胞创造了一个类似老年的炎症微环境，反映了与衰老有关的炎症（inflammageing），并阻止了干细胞的增殖和再生。

减少衰老细胞的负担，或通过CD36中和来减少它们的炎症分泌组，可加速年轻和年老小鼠的再生。相反，移植衰老细胞会延迟再生。这些研究结果提供了一种分离体内衰老细胞的技术，定义了肌肉的衰老蓝图，并发现了衰老细胞和干细胞在再生微环境中可以克服的非生产性功能相互作用。由于衰老细胞也在人类肌肉中积累，这个发现为改善整个生命中的肌肉修复开辟了潜在的道路。

据悉，组织再生需要驻留干细胞和局部微环境细胞之间的协调。

附：英文原文

Title: Senescence atlas reveals an aged-like inflamed niche that blunts muscle regeneration

Author: Moiseeva, Victoria, Cisneros, Andrs, Sica, Valentina, Deryagin, Oleg, Lai, Yiwei, Jung, Sascha, Andrs, Eva, An, Juan, Segals, Jessica, Ortet, Laura, Lukesova, Vera, Volpe, Giacomo, Benguria, Alberto, Dopazo, Ana, Aznar-Benitah, Salvador, Urano, Yasuteru, del Sol, Antonio, Esteban, Miguel A., Ohkawa, Yasuyuki, Serrano, Antonio L., Perdiguero, Eusebio, Muoz-Cnoves, Pura

Issue&Volume: 2022-12-21

Abstract: Tissue regeneration requires coordination between resident stem cells and local niche cells1,2. Here we identify that senescent cells are integral components of the skeletal muscle regenerative niche that repress regeneration at all stages of life. The technical limitation of senescent-cell scarcity3 was overcome by combining single-cell transcriptomics and a senescent-cell enrichment sorting protocol. We identified and isolated different senescent cell types from damaged muscles of young and old mice. Deeper transcriptome, chromatin and pathway analyses revealed conservation of cell identity traits as well as two universal senescence hallmarks (inflammation and fibrosis) across cell type, regeneration time and ageing. Senescent cells create an aged-like inflamed niche that mirrors inflammation associated with ageing (inflammageing4) and arrests stem cell proliferation and regeneration. Reducing the burden of senescent cells, or reducing their inflammatory secretome through CD36 neutralization, accelerates regeneration in young and old mice. By contrast, transplantation of senescent cells delays regeneration. Our results provide a technique for isolating in vivo senescent cells, define a senescence blueprint for muscle, and uncover unproductive functional interactions between senescent cells and stem cells in regenerative niches that can be overcome. As senescent cells also accumulate in human muscles, our findings open potential paths for improving muscle repair throughout life.

DOI: 10.1038/s41586-022-05535-x

Source: https://www.nature.com/articles/s41586-022-05535-x

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
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