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. 2022 Dec 21;613(7942):169–178. doi: 10.1038/s41586-022-05535-x

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© The Author(s) 2022, corrected publication 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Extended Data Fig. 10 — a) Scheme indicating the number of upregulated SASP genes in SCs, FAPs, and MCs from young and old mice at 3 and 7 d.p.i. (FDR <0.05). b) Clusters of gene sets enriched in SASP-related genes from Sen SCs, FAPs, and MCs from old mice at 3 d.p.i. (g:Profiler web server, FDR <0.05). Node size is proportional to the number of genes identified in each gene set. Grey edges indicate gene overlap. SASP genes were identified using different published databases (see methods). Differentially upregulated genes (FDR < 0.05) were considered as “SASP genes” when overexpressed in Sen populations vs their NSen counterparts. c) Heatmap of upregulated SASP genes in Sen SCs, FAPs and MCs from young and old mice at 3 and 7 d.p.i. (FDR <0.05 in at least 8/12 comparisons). d) SPiDER⁺ and SPiDER^– SCs, FAPs and MCs, freshly sorted from regenerating muscle tissue at 3 d.p.i., were cultured for 24 h in serum-deprived media, conditioned media collected, and protein levels assessed by cytokine array (n = pool of 4 mice/group). Graphs show the top 10 proteins whose levels were increased in SPiDER⁺ cells (compared to the SPiDER^–). e) Cytokine array of freshly sorted SPiDER⁺ or SPiDER^– cells from regenerating muscle at 3 d.p.i. from young or old mice cultured for 24 hours in serum-deprived media, then the conditioned media were collected and the levels of the indicated protein were assessed. Graphs represent the top 10 proteins whose levels were increased in the comparison (n = pool of 4 mice/group). f) (left) Cytokine array analysis of whole muscle secretome from (top) resting (basal) muscles comparing old and young mice, and (bottom) injured compared to basal muscles from young mice (n = pool of 2 mice/group). Graphs represent the top 10 proteins whose levels were increased in the comparison. (right) Venn-diagram showing the overlap between secreted proteins during ageing, injury-induced regeneration and secreted proteins by isolated young SPiDER⁺ cells in e. Common secreted proteins are indicated.

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