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New label-free automated survival assays reveal unexpected stress resistance patterns during C. elegans aging.

Authors
  • Benedetto, Alexandre1, 2
  • Bambade, Timothée1
  • Au, Catherine1, 2
  • Tullet, Jennifer M A1, 3
  • Monkhouse, Jennifer2
  • Dang, Hairuo1
  • Cetnar, Kalina1
  • Chan, Brian4
  • Cabreiro, Filipe1, 5
  • Gems, David1
  • 1 Department of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College London, London, UK.
  • 2 Division of Biomedical and Life Sciences, Lancaster University, Lancaster, UK.
  • 3 School of Biosciences, University of Kent, Canterbury, UK.
  • 4 Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester, UK.
  • 5 MRC London Institute of Medical Sciences, Imperial College London, London, UK.
Type
Published Article
Journal
Aging cell
Publication Date
Oct 01, 2019
Volume
18
Issue
5
Identifiers
DOI: 10.1111/acel.12998
PMID: 31309734
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Caenorhabditis elegans is an excellent model for high-throughput experimental approaches but lacks an automated means to pinpoint time of death during survival assays over a short time frame, that is, easy to implement, highly scalable, robust, and versatile. Here, we describe an automated, label-free, high-throughput method using death-associated fluorescence to monitor nematode population survival (dubbed LFASS for label-free automated survival scoring), which we apply to severe stress and infection resistance assays. We demonstrate its use to define correlations between age, longevity, and severe stress resistance, and its applicability to parasitic nematodes. The use of LFASS to assess the effects of aging on susceptibility to severe stress revealed an unexpected increase in stress resistance with advancing age, which was largely autophagy-dependent. Correlation analysis further revealed that while severe thermal stress resistance positively correlates with lifespan, severe oxidative stress resistance does not. This supports the view that temperature-sensitive protein-handling processes more than redox homeostasis underpin aging in C. elegans. That the ages of peak resistance to infection, severe oxidative stress, heat shock, and milder stressors differ markedly suggests that stress resistance and health span do not show a simple correspondence in C. elegans. © 2019 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.

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