High-throughput imaging of Caenorhabditis elegans aging using collective activity monitoring

Abstract

The genetic manipulability and short lifespan of C. elegans make it an important model for aging research. Widely applied methods for measurements of worm aging based on manual observation are labor intensive and low-throughput. Here, we describe the Worm Collective Activity Monitoring Platform (WormCamp), a system for assaying aging in C. elegans by monitoring activity of populations of worms in standard 24-well plates. We show that metrics based on the rate of decline in collective activity can be used to estimate the average lifespan and locomotor healthspan in the population. Using the WormCamp, we assay a panel of highly divergent natural isolates of C. elegans and show that both lifespan and locomotor healthspan display substantial heritability. To facilitate analysis of large numbers of worms, we developed a robotic imaging system capable of simultaneous automated monitoring of activity, lifespan, and locomotor healthspan in up to 2,304 populations containing a total of ~90,000 animals. We applied the automated system to conduct a large-scale RNA interference screen for genes that affect lifespan and locomotor healthspan. The WormCamp system is complementary to other current automated methods for assessing C. elegans aging and is well suited for efficiently screening large numbers of conditions.

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

“…Interestingly, a hybrid system is conceptually straightforward: their arrangement of five 96-well plates fits comfortably within the area of a single Observatory tray. In contrast, the WormCamp ( Fouad et al, 2021 ) system makes tradeoffs to go faster: they use a stage-mounted camera assembly to traverse over a large field of 24-well plates, giving them access to roughly 4× more wells than the Observatory holds plates but with reduced assay time (5 min compared to 9 in the Observatory) and activity only scored at the population level, not animal-by-animal. For our purposes, the C. elegans Observatory strikes the right balance between throughput and power to detect behavioral phenotypes, but other systems that push the outer edge of the throughput-precision space also have considerable potential to expand our understanding of the aging process.…”

“…Interestingly, a hybrid system is conceptually straightforward: their arrangement of five 96-well plates fits comfortably within the area of a single Observatory tray. In contrast, the WormCamp (Fouad et al, 2021) system makes tradeoffs to go faster: they use a stage-mounted camera assembly to traverse over a large field of 24-well plates, giving them access to roughly 4× more wells than FIGURE 10 detectable motility are named (cdc-42, scav-1, and scav-2). Experiment averages (blue) and random control sets (gray) for data in (A).…”

Automated multimodal imaging ofCaenorhabditis elegansbehavior in multi-well plates

“…To address these limitations, researchers have developed systems for analyzing worm behaviors via video recording and software analysis (7,8). These include methods for imaging worms on standard agar plates (9)(10)(11)(12)(13)(14)(15), in microfluidic devices (16)(17)(18)(19)(20)(21), and in multiwell substrates (1,(22)(23)(24)(25)(26).…”