Fig 1: Nematodal and mammalian Grainyhead TFs are linked to aging and insulin signaling.a Activation of the GRHL reporter without (scramble control) or with concomitant knockdown of PIK3C2A by shRNA and indicated treatments (NT = no treatment, DMSO = vehicle control, Papav = papaverine at 10 or 20 µM; n = 6 for all). b Lifespan assay of wild-type (WT) N2 nematodes on post-developmental piki-1 RNAi compared to control vector L4440. Both conditions additionally treated with 10 µM papaverine or DMSO control. c RT-qPCR of grh-1, in WT (N2) vs. a daf-2 or age-1 mutant strain (n = 3 for all). d–f Lifespan assays with a daf-2 (d), age-1 (e), or daf-16 (f) mutant strain on post-developmental grh-1 RNAi compared to control vector L4440. g Spearman’s rho correlation between Grhl1 expression in muscle (Z-score normalized) and mean lifespan of chow and high-fat diet-fed mice from the BXD mouse genetic reference population. h Similar as in (g), depicting the correlation of Grhl1 expression in muscle with area under the curve (AUC) glycemia during oral glucose tolerance test (oGTT). i Pearson’s r correlation coefficients between GRHL1 and genes in GO term ‘Insulin receptor signaling pathway’ (GO: 0008286) in human muscle samples, derived from the GTEx database. Gray bars represent non-significant correlations (P-value > 0.05). j Spearman’s rank rho correlation between GRHL1 expression in human skeletal muscle and age at natural death from the GTEx v8 dataset (n = 621). k Spearman’s rank rho correlation between GRHL1 expression in human skeletal muscle and fasting blood glucose in the entire FUSION cohort (All) or in individuals with impaired glucose tolerance (IGT) or type 2 diabetes (T2D). Color of dots indicates IGT individuals (light blue), T2D individuals (blue), and individuals belonging to neither group (black). Data in bar graphs are mean ± SEM, with sample sizes as stated and individual data points representing biological replicates. P-values were determined with two-tailed unequal variances t-tests of the indicated comparisons of unpaired control vs. treatment groups. P-values of C. elegans lifespan assays were determined by log-rank test. See Supplementary Data 1 for detailed lifespan assay statistics. Source data are provided as a Source data file.