Final published version
Licence: CC BY: Creative Commons Attribution 4.0 International License
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - New label-free automated survival assays reveal unexpected stress resistance patterns during C. elegans aging
AU - Benedetto, Alexandre
AU - Bambade, Timothée
AU - Au, Catherine
AU - Tullet, Jennifer M.A.
AU - Monkhouse, Jennifer
AU - Dang, Hairuo
AU - Cetnar, Kalina
AU - Chan, Brian
AU - Cabreiro, Filipe
AU - Gems, David
PY - 2019/10/1
Y1 - 2019/10/1
N2 - 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.
AB - 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.
KW - aging
KW - autophagy
KW - C. elegans
KW - infection
KW - stress
KW - survival
U2 - 10.1111/acel.12998
DO - 10.1111/acel.12998
M3 - Journal article
C2 - 31309734
AN - SCOPUS:85071662444
VL - 18
JO - Aging Cell
JF - Aging Cell
SN - 1474-9718
IS - 5
M1 - e12998
ER -