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.
Highlights
Interventions that can promote healthy human aging are likely to emerge from experimental studies performed with model organisms
To compare Caenorhabditis survivorship results from manual assays with results obtained from Automated Lifespan Machines (ALMs), we utilized a study design similar to that employed in our published manual assays, which comprised 22 strains of Caenorhabditis spanning three species (Lucanic et al 2017)
For the ALM study, each strain was setup for survival analysis using three independent trials, with each cohort containing over 100 animals
Summary
Interventions that can promote healthy human aging are likely to emerge from experimental studies performed with model organisms. Metformin and rapamycin, current prominent candidate interventions for the betterment of human aging, were both first observed to extend the lifespan of laboratory animals (Harrison et al 2009; Onken and Driscoll 2010). Extensive work in the field is devoted to testing compounds for the ability to extend Caenorhabditis elegans’ lifespan and healthspan (Castillo-Quan et al 2015; Maglioni et al 2016). By their very nature, experiments that test compounds for impact on lifespan and/or healthspan are time-consuming and expensive, even in model organisms.
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