Impact of genetic background and experimental reproducibility on identifying chemical compounds with robust longevity effects

Mark Lucanic, W. Todd Plummer, Esteban Chen, Jailynn Harke, Anna C. Foulger, Brian Onken, Anna L. Coleman-Hulbert, Kathleen J. Dumas, Suzhen Guo, Erik Johnson, Dipa Bhaumik, Jian Xue, Anna B. Crist, Michael P. Presley, Girish Harinath, Christine A. Sedore, Manish Chamoli, Shaunak Kamat, Michelle K. Chen, Suzanne Angeli, Christina Chang, John H. Willis, Daniel Edgar, Mary Anne Royal, Elizabeth A. Chao, Shobhna Patel, Theo Garrett, Carolina Ibanez-Ventoso, June Hope, Jason L Kish, Max Guo, Gordon J. Lithgow (), Monica Driscoll () and Patrick C. Phillips ()
Additional contact information
Mark Lucanic: The Buck Institute for Research on Aging
W. Todd Plummer: The Buck Institute for Research on Aging
Esteban Chen: Nelson Biological Laboratories, Rutgers University
Jailynn Harke: Institute of Ecology and Evolution, University of Oregon
Anna C. Foulger: The Buck Institute for Research on Aging
Brian Onken: Nelson Biological Laboratories, Rutgers University
Anna L. Coleman-Hulbert: Institute of Ecology and Evolution, University of Oregon
Kathleen J. Dumas: The Buck Institute for Research on Aging
Suzhen Guo: Nelson Biological Laboratories, Rutgers University
Erik Johnson: Institute of Ecology and Evolution, University of Oregon
Dipa Bhaumik: The Buck Institute for Research on Aging
Jian Xue: Nelson Biological Laboratories, Rutgers University
Anna B. Crist: Institute of Ecology and Evolution, University of Oregon
Michael P. Presley: The Buck Institute for Research on Aging
Girish Harinath: Nelson Biological Laboratories, Rutgers University
Christine A. Sedore: Institute of Ecology and Evolution, University of Oregon
Manish Chamoli: The Buck Institute for Research on Aging
Shaunak Kamat: Nelson Biological Laboratories, Rutgers University
Michelle K. Chen: Institute of Ecology and Evolution, University of Oregon
Suzanne Angeli: The Buck Institute for Research on Aging
Christina Chang: Nelson Biological Laboratories, Rutgers University
John H. Willis: Institute of Ecology and Evolution, University of Oregon
Daniel Edgar: The Buck Institute for Research on Aging
Mary Anne Royal: Nelson Biological Laboratories, Rutgers University
Elizabeth A. Chao: The Buck Institute for Research on Aging
Shobhna Patel: Nelson Biological Laboratories, Rutgers University
Theo Garrett: The Buck Institute for Research on Aging
Carolina Ibanez-Ventoso: Nelson Biological Laboratories, Rutgers University
June Hope: The Buck Institute for Research on Aging
Jason L Kish: The Buck Institute for Research on Aging
Max Guo: National Institute on Aging
Gordon J. Lithgow: The Buck Institute for Research on Aging
Monica Driscoll: Nelson Biological Laboratories, Rutgers University
Patrick C. Phillips: Institute of Ecology and Evolution, University of Oregon

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: Abstract Limiting the debilitating consequences of ageing is a major medical challenge of our time. Robust pharmacological interventions that promote healthy ageing across diverse genetic backgrounds may engage conserved longevity pathways. Here we report results from the Caenorhabditis Intervention Testing Program in assessing longevity variation across 22 Caenorhabditis strains spanning 3 species, using multiple replicates collected across three independent laboratories. Reproducibility between test sites is high, whereas individual trial reproducibility is relatively low. Of ten pro-longevity chemicals tested, six significantly extend lifespan in at least one strain. Three reported dietary restriction mimetics are mainly effective across C. elegans strains, indicating species and strain-specific responses. In contrast, the amyloid dye ThioflavinT is both potent and robust across the strains. Our results highlight promising pharmacological leads and demonstrate the importance of assessing lifespans of discrete cohorts across repeat studies to capture biological variation in the search for reproducible ageing interventions.

Date: 2017
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14256

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DOI: 10.1038/ncomms14256

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