Journal Article

Longitudinal imaging of Caenorhabditis elegans in a microfabricated device reveals variation in behavioral decline during aging

Churgin, Matthew A, Jung, Sang-Kyu, Fang-Yen, Christopher, Chen, Xiangmei, Raizen, David M, Yu, Chih-Chieh

2017

Overview

The roundworm C. elegans is a mainstay of aging research due to its short lifespan and easily manipulable genetics. Current, widely used methods for long-term measurement of C. elegans are limited by low throughput and the difficulty of performing longitudinal monitoring of aging phenotypes. Here we describe the WorMotel, a microfabricated device for long-term cultivation and automated longitudinal imaging of large numbers of C. elegans confined to individual wells. Using the WorMotel, we find that short-lived and long-lived strains exhibit patterns of behavioral decline that do not temporally scale between individuals or populations, but rather resemble the shortest and longest lived individuals in a wild type population. We also find that behavioral trajectories of worms subject to oxidative stress resemble trajectories observed during aging. Our method is a powerful and scalable tool for analysis of C. elegans behavior and aging. Aging affects almost all living things, yet little is known about the biological changes that occur as we get older. Scientists often study aging in the microscopic roundworm Caenorhabditis elegans because it reproduces quickly and its lifespan is short (about 2–3 weeks on average). To date, investigations have helped to reveal genes that affect overall lifespan. However, it is not known how much these genes also affect the animal’s healthy lifespan or “healthspan”, that is to say, the length of time before advancing age begins to negatively affect health. Until now, studies with worms have often been limited because measuring health and aging required time-consuming and difficult manual experiments. This also meant that worms were studied together as groups, rather than as individuals, providing a simplified picture of what was going on. An automated system in which many single worms can be analyzed and assessed would provide a much more detailed view of the effects of aging on health. Churgin et al. have now developed a device called the WorMotel to allow simultaneous automated examination of 240 worms throughout their entire adult lifespan. The WorMotel is a rectangular slab of clear silicone rubber with small wells in it. A single worm is confined in each well with a source of bacteria for food, and a camera is used to track and monitor each worm’s behavior over time. This device confirmed that worms move more slowly as they get older, which was taken to be a measurement of the worms’ declining health. Worms that lived the longest declined over the first few days and then had a long plateau of very low activity before eventually dying. Short-lived worms became slower and died fairly promptly. Churgin et al. also showed that the worms with mutations that increase lifespan declined in a similar way to the longest-lived normal worms, and that mutants with shorter lifespans declined like the shortest-lived normal worms. Also, normal worms that had been exposed to a chemical called paraquat – which stresses the worm's cells and shortens the worm’s lifespans to a few days – slowed down in a similar manner as aging worms, suggesting that the stress is similar to the aging process. Tools like the WorMotel can improve our understanding of the links between lifespan and healthspan. The tool is designed to be versatile and can be used with standard imaging systems and automated tools, meaning it can be scaled up to deal with tens of thousands of worms at once. Churgin et al. are now using the WorMotel to find other genes that influence healthspan and understand how they contribute to deteriorating health as animals age. Aging affects us all and learning more about healthspan could lead to drugs or interventions to help more people to live healthily for longer.

• Publisher: eLife Science Publications, Ltd,eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
• Subject: Aging / Aging (Biology) / Animals / Automation / Bacteria / Behavior / Behavior, Animal / Caenorhabditis elegans / Caenorhabditis elegans - genetics / Caenorhabditis elegans - physiology / Design / Experiments / Genes and Chromosomes / Geometry / healthspan / Hydrogels / Life span / lifespan / Longitudinal Studies / Medical research / Methods / Neuroscience / Observations / Optical Imaging - instrumentation / Optical Imaging - methods / Oxidative stress / Parasitology - instrumentation / Parasitology - methods / Phenotype / Physiological aspects / stress resistance / Tools and Resources / WorMotel