Automated lifespan determination across Caenorhabditis strains and species reveals assay-specific effects of chemical interventions
Open Access
- 10 December 2019
- journal article
- research article
- Published by Springer Science and Business Media LLC in GeroScience
- Vol. 41 (6), 945-960
- https://doi.org/10.1007/s11357-019-00108-9
Abstract
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.Keywords
Funding Information
- National Institute on Aging (U01 AG045829, U24 AG056052, U01 AG045864, U01 AG045844, R21 AG048528, R01 AG029631, UL1RR024917)
- Larry L. Hillblom Foundation
- Glenn Foundation for Medical Research
This publication has 21 references indexed in Scilit:
- The Stress-Chip: A microfluidic platform for stress analysis in Caenorhabditis elegansPLOS ONE, 2019
- Visible light reduces C. elegans longevityNature Communications, 2018
- Comparative Degradation of a Thiazole Pollutant by an Advanced Oxidation Process and an Enzymatic ApproachBiomolecules, 2017
- A long journey to reproducible resultsNature, 2017
- Impact of genetic background and experimental reproducibility on identifying chemical compounds with robust longevity effectsNature Communications, 2017
- Chemical activation of a food deprivation signal extends lifespanAging Cell, 2016
- Genetics and Pharmacology of LongevityPublished by Elsevier BV ,2015
- The metabolite α-ketoglutarate extends lifespan by inhibiting ATP synthase and TORNature, 2014
- Amyloid-binding compounds maintain protein homeostasis during ageing and extend lifespanNature, 2011
- Rapamycin fed late in life extends lifespan in genetically heterogeneous miceNature, 2009