2026-04-20T01:47:10Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/164702024-09-27T07:57:20Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Moiseeva, Victoria author Cisneros, Andrés author Sica, Valentina author Deryagin, Oleg author Lai, Yiwei author Jung, Sascha author Andrés, Eva author An, Juan author Segalés, Jessica author Ortet, Laura author Lukesova, Vera author Volpe, Giacomo author Benguria, Alberto author Dopazo, Ana author Benitah, Salvador Aznar author Urano, Yasuteru author Del Sol, Antonio author Esteban, Miguel A author Ohkawa, Yasuyuki author Serrano, Antonio L author Perdiguero, Eusebio author Munoz-Canoves, Pura author 2023-01 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. Nature. 2023 Jan;613(7942):169-178. http://hdl.handle.net/20.500.12105/16470 36544018 10.1038/s41586-022-05535-x 1476-4687 Nature Senescence atlas reveals an aged-like inflamed niche that blunts muscle regeneration.