The C. elegans Observatory: High-throughput exploration of behavioral aging

Abstract

Organisms undergo a variety of characteristic changes as they age, suggesting a substantial commonality in the mechanistic basis of aging. Experiments in model organisms have revealed a variety of cellular systems that impact lifespan, but technical challenges have prevented a comprehensive evaluation of how these components impact the trajectory of aging, and many components likely remain undiscovered. To facilitate the deeper exploration of aging trajectories at a sufficient scale to enable primary screening, we have created the Caenorhabditis elegans Observatory, an automated system for monitoring the behavior of group-housed C. elegans throughout their lifespans. One Observatory consists of a set of computers running custom software to control an incubator containing custom imaging and motion-control hardware. In its standard configuration, the Observatory cycles through trays of standard 6 cm plates, running four assays per day on up to 576 plates per incubator. High-speed image processing captures a range of behavioral metrics, including movement speed and stimulus-induced turning, and a data processing pipeline continuously computes summary statistics. The Observatory software includes a web interface that allows the user to input metadata and view graphs of the trajectory of behavioral aging as the experiment unfolds. Compared to the manual use of a plate-based C. elegans tracker, the Observatory reduces the effort required by close to two orders of magnitude. Within the Observatory, reducing the function of known lifespan genes with RNA interference (RNAi) gives the expected phenotypic changes, including extended motility in daf-2(RNAi) and progeria in hsf-1(RNAi). Lifespans scored manually from worms raised in conventional conditions match those scored from images captured by the Observatory. We have used the Observatory for a small candidate-gene screen and identified an extended youthful vigor phenotype for tank-1(RNAi) and a progeric phenotype for cdc-42(RNAi). By utilizing the Observatory, it is now feasible to conduct whole-genome screens for an aging-trajectory phenotype, thus greatly increasing our ability to discover and analyze new components of the aging program.

CeLab, a Microfluidic Platform for the Study of Life History Traits, reveals Metformin and SGK-1 regulation of Longevity and Reproductive Span

“…Some of these challenges have been met by long-term culturing and imaging 2,3 that have been used for large-scale lifespan analyses 4–6 . For example, a recent high-throughput analysis of lifespan and motility traits 7 re-emphasized that induced Maximum Velocity best reflects health of individuals with age, as we previously reported 8 . However, such large-scale approaches usually require the elimination of progeny, limiting the analysis to lifespan and healthspan metrics that ignore reproductive traits and reproductive effects on lifespan.…”

CeLab, a microfluidic platform for the study of life history traits, reveals metformin and SGK-1 regulation of longevity and reproductive span

“…1 Some of these challenges have been met by long-term culturing and imaging 2,3 that have been used for large-scale lifespan analyses. [4][5][6] For example, a recent highthroughput analysis of lifespan and motility traits 7 reemphasized that induced maximum velocity best reflects health of individuals with age, as we previously reported. 8 However, such large-scale approaches usually require the elimination of progeny, limiting the analysis to lifespan and healthspan metrics that ignore reproductive traits and reproductive effects on lifespan.…”

Worm Generator: A System for High-Throughput in Vivo Screening

“…Moreover, our high-throughput fabrication methods also made it easy and low-cost for mass production of HB-TENG devices. Importantly, compared to the previous methods for monitoring the intact small animals’ behaviors by optical imaging, our platform directly converted C. elegans behavioral activities to information-rich electrical readouts and avoided the experimental artifacts that imposed by the optical stimuli. , …”

“…Importantly, compared to the previous methods for monitoring the intact small animals' behaviors by optical imaging, our platform directly converted C. elegans behavioral activities to information-rich electrical readouts and avoided the experimental artifacts that imposed by the optical stimuli. 47,48 Though the concept of drug screening strategy using behavioral fingerprints had previously been reported, their systems still focused on the images based behavioral readouts. 51 The most important advance of this work is the development of a practically functional device that greatly increases the electrical outputs of small animals.…”

“…Microfluidic devices and tracker systems coupling with optical detection platforms have recently emerged as powerful tools for high-throughput behavioral profiling of C. elegans . ,,,, Systems with micropillar arrays were also proposed to enable measurement of muscular strength and drug tests. , It is worth noting, however, that most of the proposed platforms required expensive microscopic equipment coupling with high-resolution cameras, sophisticated fluidic switching modules, and tedious image processing. In this proof-of-concept study, the TENG-based system, which only required a simple electrical recording module, was demonstrated for behavioral monitoring of the intact small animals.…”