PT - JOURNAL ARTICLE AU - Stephen A. Banse AU - Christine A. Sedore AU - Erik Johnson AU - Anna L. Coleman-Hulbert AU - Brian Onken AU - David Hall AU - E. Grace Jackson AU - Phu Huynh AU - Anna C. Foulger AU - Suzhen Guo AU - Theo Garrett AU - Jian Xue AU - Delaney Inman AU - Mackenzie L. Morshead AU - W. Todd Plummer AU - Esteban Chen AU - Dipa Bhaumik AU - Michelle K. Chen AU - Girish Harinath AU - Manish Chamoli AU - Rose P. Quinn AU - Ron Falkowski AU - Daniel Edgar AU - Madeline O. Schmidt AU - Mark Lucanic AU - Max Guo AU - Monica Driscoll AU - Gordon J. Lithgow AU - Patrick C. Phillips TI - Antioxidants green tea extract and nordihydroguaiaretic acid confer species and strain specific lifespan and health effects in <em>Caenorhabditis</em> nematodes AID - 10.1101/2021.11.09.464847 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.11.09.464847 4099 - http://biorxiv.org/content/early/2021/11/10/2021.11.09.464847.short 4100 - http://biorxiv.org/content/early/2021/11/10/2021.11.09.464847.full AB - The Caenorhabditis Intervention Testing Program (CITP) is an NIH-funded research consortium of investigators who conduct analyses at three independent sites to identify chemical interventions that reproducibly promote health and lifespan in a robust manner. The founding principle of the CITP is that compounds with positive effects across a genetically diverse panel of Caenorhabditis species and strains are likely engaging conserved biochemical pathways to exert their effects. As such, interventions that are broadly efficacious might be considered prominent compounds for translation for pre-clinical research and human clinical applications. Here, we report results generated using a recently streamlined pipeline approach for the evaluation of the effects of chemical compounds on lifespan and health. We studied five compounds previously shown to extend C. elegans lifespan or thought to promote mammalian health: 17α-estradiol, acarbose, green tea extract, nordihydroguaiaretic acid, and rapamycin. We found that green tea extract and nordihydroguaiaretic acid extend Caenorhabditis lifespan in a species-specific manner. Additionally, these two antioxidants conferred assay-specific effects in some studies—for example, decreasing survival for certain genetic backgrounds in manual survival assays in contrast with extended lifespan as assayed using automated C. elegans Lifespan Machines. We also observed that GTE and NDGA impact on older adult mobility capacity is dependent on genetic background, and that GTE reduces oxidative stress resistance in some Caenorhabditis strains. Overall, our analysis of the five compounds supports the general idea that genetic background and assay type can influence lifespan and health effects of compounds, and underscores that lifespan and health can be uncoupled by chemical interventions.Competing Interest StatementThe authors have declared no competing interest.