Regulons were identified in SCENIC v0.1.6 package in R (43). We used expression data pertaining to cells from old mice. Only genes with at least one raw count in at least one cell were analyzed throughout the pipeline. All gene raw counts were then log-transformed. Regulons were identified by SCENIC only if they were found to be active in more than 1% of all cells and correlated with at least one other regulon (|r| > 0.3). In downstream analysis, we focused on high-confidence regulons, which we defined as active in more than 10% of the cells in at least one of the subsets in all mice and including high-confidence relationships between the transcription factor and at least nine target genes.

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