INS and neoplasm: Gene Set Enrichment Analyses (GSEA) showed significant downregulation of gene sets known to mediate the effects of CR on life span and tumor growth9,10,30–33, such as the Myc signaling pathways, and targets of insulin/IGF1 signaling (Fig. 2b), including the immediate-early response genes Fos, Jun, Egr1, Egr2, Nr4a1, Atf3, Socs3 (Supplementary Fig. 3a), consistent with the reduced circulating levels of IGF1 in CR-fed APL mice6,7 (Supplementary Fig. 3b).