Automated lifespan determination across Caenorhabditis strains and species reveals assay-specific effects of chemical interventions.

Autor: Banse SA; Institute of Ecology and Evolution, University of Oregon, Eugene, OR, 97403, USA., Lucanic M; The Buck Institute for Research on Aging, Novato, CA, 94945, USA., Sedore CA; Institute of Ecology and Evolution, University of Oregon, Eugene, OR, 97403, USA., Coleman-Hulbert AL; Institute of Ecology and Evolution, University of Oregon, Eugene, OR, 97403, USA., Plummer WT; The Buck Institute for Research on Aging, Novato, CA, 94945, USA., Chen E; Department of Molecular Biology and Biochemistry, Nelson Biological Laboratories, Rutgers University, Piscataway, NJ, 08854, USA., Kish JL; The Buck Institute for Research on Aging, Novato, CA, 94945, USA., Hall D; The Buck Institute for Research on Aging, Novato, CA, 94945, USA., Onken B; Department of Molecular Biology and Biochemistry, Nelson Biological Laboratories, Rutgers University, Piscataway, NJ, 08854, USA., Presley MP; The Buck Institute for Research on Aging, Novato, CA, 94945, USA., Jones EG; Institute of Ecology and Evolution, University of Oregon, Eugene, OR, 97403, USA., Blue BW; Institute of Ecology and Evolution, University of Oregon, Eugene, OR, 97403, USA., Garrett T; The Buck Institute for Research on Aging, Novato, CA, 94945, USA., Abbott M; Department of Molecular Biology and Biochemistry, Nelson Biological Laboratories, Rutgers University, Piscataway, NJ, 08854, USA., Xue J; Department of Molecular Biology and Biochemistry, Nelson Biological Laboratories, Rutgers University, Piscataway, NJ, 08854, USA., Guo S; Department of Molecular Biology and Biochemistry, Nelson Biological Laboratories, Rutgers University, Piscataway, NJ, 08854, USA., Johnson E; Institute of Ecology and Evolution, University of Oregon, Eugene, OR, 97403, USA., Foulger AC; The Buck Institute for Research on Aging, Novato, CA, 94945, USA., Chamoli M; The Buck Institute for Research on Aging, Novato, CA, 94945, USA., Falkowski R; Department of Molecular Biology and Biochemistry, Nelson Biological Laboratories, Rutgers University, Piscataway, NJ, 08854, USA., Melentijevic I; Department of Molecular Biology and Biochemistry, Nelson Biological Laboratories, Rutgers University, Piscataway, NJ, 08854, USA., Harinath G; Department of Molecular Biology and Biochemistry, Nelson Biological Laboratories, Rutgers University, Piscataway, NJ, 08854, USA., Huynh P; Department of Molecular Biology and Biochemistry, Nelson Biological Laboratories, Rutgers University, Piscataway, NJ, 08854, USA., Patel S; Department of Molecular Biology and Biochemistry, Nelson Biological Laboratories, Rutgers University, Piscataway, NJ, 08854, USA., Edgar D; The Buck Institute for Research on Aging, Novato, CA, 94945, USA., Jarrett CM; Institute of Ecology and Evolution, University of Oregon, Eugene, OR, 97403, USA., Guo M; Division of Aging Biology, National Institute on Aging, Bethesda, MD, 20892-9205, USA., Kapahi P; The Buck Institute for Research on Aging, Novato, CA, 94945, USA., Lithgow GJ; The Buck Institute for Research on Aging, Novato, CA, 94945, USA. glithgow@buckinstitute.org., Driscoll M; Department of Molecular Biology and Biochemistry, Nelson Biological Laboratories, Rutgers University, Piscataway, NJ, 08854, USA. driscoll@dls.rutgers.edu., Phillips PC; Institute of Ecology and Evolution, University of Oregon, Eugene, OR, 97403, USA. pphil@uoregon.edu.
Jazyk: angličtina
Zdroj: GeroScience [Geroscience] 2019 Dec; Vol. 41 (6), pp. 945-960. Date of Electronic Publication: 2019 Dec 10.
DOI: 10.1007/s11357-019-00108-9
Abstrakt: The goal of the Caenorhabditis Intervention Testing Program is to identify robust and reproducible pro-longevity interventions that are efficacious across genetically diverse cohorts in the Caenorhabditis genus. The project design features multiple experimental replicates collected by three different laboratories. Our initial effort employed fully manual survival assays. With an interest in increasing throughput, we explored automation with flatbed scanner-based Automated Lifespan Machines (ALMs). We used ALMs to measure survivorship of 22 Caenorhabditis strains spanning three species. Additionally, we tested five chemicals that we previously found extended lifespan in manual assays. Overall, we found similar sources of variation among trials for the ALM and our previous manual assays, verifying reproducibility of outcome. Survival assessment was generally consistent between the manual and the ALM assays, although we did observe radically contrasting results for certain compound interventions. We found that particular lifespan outcome differences could be attributed to protocol elements such as enhanced light exposure of specific compounds in the ALM, underscoring that differences in technical details can influence outcomes and therefore interpretation. Overall, we demonstrate that the ALMs effectively reproduce a large, conventionally scored dataset from a diverse test set, independently validating ALMs as a robust and reproducible approach toward aging-intervention screening.
Databáze: MEDLINE