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. 2022 Jan 10;13:107. doi: 10.1038/s41467-021-27732-4

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© The Author(s) 2022

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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 3 — a Overview of impact of the respective compound (cpd) on lifespan of wild-type (WT) N2 nematodes at 1 µM in plate, as percentage change of mean lifespan vs. control treatment with DMSO (ctrl). Also see Fig. 2c–q. b Activation of GRHL reporter by the top 3 lifespan-extending compounds from (a) (Vstat = vorinostat, Papav = papaverine, Piperl = piperlongumine) at 5–10 µM in the presence (wild-type reporter with n = 4) or absence (two independent deletion reporters with n = 8 combined) of GRHL1. c, d Lifespan assays of vorinostat at 0.1 (c) or 10 µM (d) in plate, using WT (N2) nematodes and vs. DMSO control. e Lifespan assay of vorinostat at 10 µM in plate, using Δgrh-1 and vs. DMSO control. f, g Similar to (c), (d), using papaverine. h Similar to (e), using papaverine at 10 µM in plate. i, j Similar to (c), (d), using piperlongumine. k Similar to (e), using piperlongumine at 0.1 µM in plate. 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. Lifespan graphs contain percentage change of mean lifespan compound vs. DMSO control and P-values as determined by log-rank test. See Supplementary Data 1 for detailed lifespan assay statistics. Source data are provided as a Source data file.