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

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. DOI: http://dx.doi.org/10.7554/eLife.26652.001

[1]  C. Fang-Yen,et al.  Food responsiveness regulates episodic behavioral states in Caenorhabditis elegans. , 2017, Journal of neurophysiology.

[2]  S. Edwards,et al.  A Novel Molecular Solution for Ultraviolet Light Detection in Caenorhabditis elegans , 2008, PLoS biology.

[3]  D. Riddle,et al.  Two pleiotropic classes of daf-2 mutation affect larval arrest, adult behavior, reproduction and longevity in Caenorhabditis elegans. , 1998, Genetics.

[4]  C. Kenyon,et al.  Stimulation of Movement in a Quiescent, Hibernation-Like Form of Caenorhabditis elegans by Dopamine Signaling , 2009, The Journal of Neuroscience.

[5]  D. Raizen,et al.  FMRFamide-like FLP-13 Neuropeptides Promote Quiescence following Heat Stress in Caenorhabditis elegans , 2014, Current Biology.

[6]  Kyle Duke,et al.  Transcriptional Profile of Aging in C. elegans , 2002, Current Biology.

[7]  Chengjie Xiong,et al.  Measurements of age-related changes of physiological processes that predict lifespan of Caenorhabditis elegans. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[8]  J. Apfeld,et al.  The AMP-activated protein kinase AAK-2 links energy levels and insulin-like signals to lifespan in C. elegans. , 2004, Genes & development.

[9]  S. Lockery,et al.  Mutations in the Caenorhabditis elegans Na,K-ATPase alpha-subunit gene, eat-6, disrupt excitable cell function , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[10]  C. Murphy,et al.  The Intersection of Aging, Longevity Pathways, and Learning and Memory in C. elegans , 2012, Front. Gene..

[11]  D. Hall,et al.  Stochastic and genetic factors influence tissue-specific decline in ageing C. elegans , 2002, Nature.

[12]  A. Eijkelenboom,et al.  FOXOs: signalling integrators for homeostasis maintenance , 2013, Nature reviews. Molecular cell biology.

[13]  D. Boomsma,et al.  Regular Exercise, Subjective Wellbeing, and Internalizing Problems in Adolescence: Causality or Genetic Pleiotropy? , 2012, Front. Gene..

[14]  T. Blackwell,et al.  SKN-1 links C. elegans mesendodermal specification to a conserved oxidative stress response. , 2003, Genes & development.

[15]  I. Martin,et al.  Functional senescence in Drosophila melanogaster , 2005, Ageing Research Reviews.

[16]  Jeong-Hoon Hahm,et al.  C. elegans maximum velocity correlates with healthspan and is maintained in worms with an insulin receptor mutation , 2015, Nature Communications.

[17]  T. Johnson,et al.  A mutation in the age-1 gene in Caenorhabditis elegans lengthens life and reduces hermaphrodite fertility. , 2002, Genetics.

[18]  Cynthia Kenyon,et al.  How a Mutation that Slows Aging Can Also Disproportionately Extend End-of-Life Decrepitude. , 2017, Cell reports.

[19]  John M. Walker,et al.  C. elegans , 2006, Methods in Molecular Biology.

[20]  Laura E. Grieneisen,et al.  Frequent Arousal from Hibernation Linked to Severity of Infection and Mortality in Bats with White-Nose Syndrome , 2012, PloS one.

[21]  E. Greer,et al.  Different dietary restriction regimens extend lifespan by both independent and overlapping genetic pathways in C. elegans , 2009, Aging cell.

[22]  J. Thomas,et al.  Neurosecretory control of aging in Caenorhabditis elegans. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[23]  J. Apfeld,et al.  The temporal scaling of Caenorhabditis elegans ageing , 2016, Nature.

[24]  Filip Ilievski,et al.  Multigait soft robot , 2011, Proceedings of the National Academy of Sciences.

[25]  S. Brenner The genetics of Caenorhabditis elegans. , 1974, Genetics.

[26]  Walter Fontana,et al.  The Caenorhabditis elegans Lifespan Machine , 2013, Nature Methods.

[27]  E. Greer,et al.  FOXO transcription factors in ageing and cancer , 2007, Acta physiologica.

[28]  D. Raizen,et al.  The RFamide receptor DMSR-1 regulates stress-induced sleep in C. elegans , 2017, eLife.

[29]  B. Lakowski,et al.  The genetics of caloric restriction in Caenorhabditis elegans. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[30]  Theresa Stiernagle Maintenance of C. elegans. , 2006, WormBook : the online review of C. elegans biology.

[31]  Christopher Fang-Yen,et al.  An Imaging System for C. elegans Behavior. , 2015, Methods in molecular biology.

[32]  Sandra L Martin,et al.  Mammalian hibernation: cellular and molecular responses to depressed metabolism and low temperature. , 2003, Physiological reviews.

[33]  C. Kenyon,et al.  A C. elegans mutant that lives twice as long as wild type , 1993, Nature.

[34]  C. Fang-Yen,et al.  The neuropeptide NLP-22 regulates a sleep-like state in Caenorhabditis elegans , 2013, Nature Communications.

[35]  G. Ruvkun,et al.  The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans , 1997, Nature.

[36]  Zhaoyang Feng,et al.  Light-sensitive neurons and channels mediate phototaxis in C. elegans , 2008, Nature Neuroscience.

[37]  J. Apfeld,et al.  Regulation of lifespan by sensory perception in Caenorhabditis elegans , 1999, Nature.

[38]  David Gems,et al.  Shared Transcriptional Signature in Caenorhabditis elegans Dauer Larvae and Long-lived daf-2 Mutants Implicates Detoxification System in Longevity Assurance* , 2004, Journal of Biological Chemistry.

[39]  Zachary Pincus,et al.  Extended Twilight among Isogenic C. elegans Causes a Disproportionate Scaling between Lifespan and Health. , 2016, Cell systems.

[40]  Hilla Peretz,et al.  Ju n 20 03 Schrödinger ’ s Cat : The rules of engagement , 2003 .

[41]  David M. Raizen,et al.  Multi-well imaging of development and behavior in Caenorhabditis elegans , 2014, Journal of Neuroscience Methods.

[42]  Jeffrey M. Hausdorff,et al.  Altered fractal dynamics of gait: reduced stride-interval correlations with aging and Huntington's disease. , 1997, Journal of applied physiology.

[43]  David M. Raizen,et al.  Lethargus is a Caenorhabditis elegans sleep-like state , 2008, Nature.