Impact of genetic background and experimental reproducibility on identifying chemical compounds with robust longevity effects
| Autor: | Carolina Ibanez-Ventoso, Monica Driscoll, Anna L. Coleman-Hulbert, Michael P. Presley, Max Guo, Jason L. Kish, Shobhna Patel, Jian Xue, Manish Chamoli, Dipa Bhaumik, Gordon J. Lithgow, Esteban Chen, Michelle K. Chen, Girish Harinath, June Hope, Anna B. Crist, Patrick C. Phillips, Shaunak Kamat, Daniel Edgar, John H. Willis, Suzhen Guo, Brian Onken, Christine A Sedore, Kathleen J. Dumas, Mark Lucanic, Suzanne Angeli, Erik Johnson, Elizabeth A. Chao, W. Todd Plummer, Anna C. Foulger, Christina Chang, Jailynn Harke, Theo Garrett, Mary Anne Royal |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Science media_common.quotation_subject Longevity General Physics and Astronomy Computational biology Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Species Specificity Biological variation Animals Benzothiazoles Organic Chemicals Caenorhabditis elegans media_common Genetics Reproducibility Multidisciplinary Dose-Response Relationship Drug biology Strain (biology) Reproducibility of Results General Chemistry Limiting biology.organism_classification 3. Good health Caenorhabditis Thiazoles Fertility 030104 developmental biology Ageing Genetic Background |
| Zdroj: | Nature Communications Nature Communications, Vol 8, Iss 1, Pp 1-13 (2017) |
| ISSN: | 2041-1723 |
| Popis: | 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. Irreproducibility of biological findings is a major challenge for drug development. Here the authors examine the lifespans of 22 worm strains in three different laboratories and the effects of ten known chemicals to assess reproducibility in the face of variations in genetic background, chemical treatment and lab environment. |
| Databáze: | OpenAIRE |
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