Stress tolerance and lifespan in C. elegans are modulated by natural allelic variation in CMK-1

L.B. Snoek, M.G. Sterken, R.P.J. Bevers, J.M. Volkers, A. van 't Hof, R. Brenchley, B. Lehner, A. Cossins, J.E. Kammenga

Research output: Contribution to conferencePosterAcademic

Abstract

Genetic control of aging in C. elegans has primarily been studied using
derived mutants of the strain N2. These mutants often display extreme
lifespan accompanied by increased stress resistance. Yet, identification of
genes that underlie variation in lifespan and stress tolerance in natural
populations remains a major challenge. We investigated gene expression
architecture and longevity and found that stress tolerance and lifespan in C.
elegans are modulated by natural allelic variation in cmk-1.
Variation in gene expression levels was linked to genomic loci (eQTL)
using fully sequenced recombinant inbred populations derived from
divergent wild-type strains N2 and CB4856. In these strains regulatory loci
were identified under standard and under heat-stress conditions. After
verification, the causal regulator was identified by screening knock-out
mutants of candidate genes. Moreover, lifespan was measured under
standard conditions and in strains that received a heat shock treatment.
We identified a major stress-related regulatory locus that affects expression
variation in more than 100 genes and one of the causal genes was found to
be cmk-1. The effects of this variation include modulation of insulin-like
signaling targets supporting a model in which allelic variation in cmk-1
regulates a subset of daf-16 targets under stress conditions, leading to
increased stress resistance and prolonged lifespan.
In conclusion, genes affecting lifespan variation in nature may not be those
identified by mutagenizing a single C. elegans strain. Our data suggests that
pathways previously associated with aging are affected, but not by the usual
suspects.
Original languageEnglish
Publication statusPublished - 31 Mar 2016
EventEvolutionary Biology of Caenorhabditis and other nematodes - Cold Spring Harbor Laboratory, Cold Spring Harbor, United States
Duration: 30 Mar 20162 Apr 2016

Conference

ConferenceEvolutionary Biology of Caenorhabditis and other nematodes
CountryUnited States
CityCold Spring Harbor
Period30/03/162/04/16

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stress tolerance
genes
heat stress
mutants
loci
genetic resistance
insulin
screening
genomics
gene expression

Cite this

Snoek, L. B., Sterken, M. G., Bevers, R. P. J., Volkers, J. M., van 't Hof, A., Brenchley, R., ... Kammenga, J. E. (2016). Stress tolerance and lifespan in C. elegans are modulated by natural allelic variation in CMK-1. Poster session presented at Evolutionary Biology of Caenorhabditis and other nematodes, Cold Spring Harbor, United States.
Snoek, L.B. ; Sterken, M.G. ; Bevers, R.P.J. ; Volkers, J.M. ; van 't Hof, A. ; Brenchley, R. ; Lehner, B. ; Cossins, A. ; Kammenga, J.E. / Stress tolerance and lifespan in C. elegans are modulated by natural allelic variation in CMK-1. Poster session presented at Evolutionary Biology of Caenorhabditis and other nematodes, Cold Spring Harbor, United States.
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title = "Stress tolerance and lifespan in C. elegans are modulated by natural allelic variation in CMK-1",
abstract = "Genetic control of aging in C. elegans has primarily been studied usingderived mutants of the strain N2. These mutants often display extremelifespan accompanied by increased stress resistance. Yet, identification ofgenes that underlie variation in lifespan and stress tolerance in naturalpopulations remains a major challenge. We investigated gene expressionarchitecture and longevity and found that stress tolerance and lifespan in C.elegans are modulated by natural allelic variation in cmk-1.Variation in gene expression levels was linked to genomic loci (eQTL)using fully sequenced recombinant inbred populations derived fromdivergent wild-type strains N2 and CB4856. In these strains regulatory lociwere identified under standard and under heat-stress conditions. Afterverification, the causal regulator was identified by screening knock-outmutants of candidate genes. Moreover, lifespan was measured understandard conditions and in strains that received a heat shock treatment.We identified a major stress-related regulatory locus that affects expressionvariation in more than 100 genes and one of the causal genes was found tobe cmk-1. The effects of this variation include modulation of insulin-likesignaling targets supporting a model in which allelic variation in cmk-1regulates a subset of daf-16 targets under stress conditions, leading toincreased stress resistance and prolonged lifespan.In conclusion, genes affecting lifespan variation in nature may not be thoseidentified by mutagenizing a single C. elegans strain. Our data suggests thatpathways previously associated with aging are affected, but not by the usualsuspects.",
author = "L.B. Snoek and M.G. Sterken and R.P.J. Bevers and J.M. Volkers and {van 't Hof}, A. and R. Brenchley and B. Lehner and A. Cossins and J.E. Kammenga",
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Snoek, LB, Sterken, MG, Bevers, RPJ, Volkers, JM, van 't Hof, A, Brenchley, R, Lehner, B, Cossins, A & Kammenga, JE 2016, 'Stress tolerance and lifespan in C. elegans are modulated by natural allelic variation in CMK-1', Cold Spring Harbor, United States, 30/03/16 - 2/04/16, .

Stress tolerance and lifespan in C. elegans are modulated by natural allelic variation in CMK-1. / Snoek, L.B.; Sterken, M.G.; Bevers, R.P.J.; Volkers, J.M.; van 't Hof, A.; Brenchley, R.; Lehner, B.; Cossins, A.; Kammenga, J.E.

2016. Poster session presented at Evolutionary Biology of Caenorhabditis and other nematodes, Cold Spring Harbor, United States.

Research output: Contribution to conferencePosterAcademic

TY - CONF

T1 - Stress tolerance and lifespan in C. elegans are modulated by natural allelic variation in CMK-1

AU - Snoek, L.B.

AU - Sterken, M.G.

AU - Bevers, R.P.J.

AU - Volkers, J.M.

AU - van 't Hof, A.

AU - Brenchley, R.

AU - Lehner, B.

AU - Cossins, A.

AU - Kammenga, J.E.

PY - 2016/3/31

Y1 - 2016/3/31

N2 - Genetic control of aging in C. elegans has primarily been studied usingderived mutants of the strain N2. These mutants often display extremelifespan accompanied by increased stress resistance. Yet, identification ofgenes that underlie variation in lifespan and stress tolerance in naturalpopulations remains a major challenge. We investigated gene expressionarchitecture and longevity and found that stress tolerance and lifespan in C.elegans are modulated by natural allelic variation in cmk-1.Variation in gene expression levels was linked to genomic loci (eQTL)using fully sequenced recombinant inbred populations derived fromdivergent wild-type strains N2 and CB4856. In these strains regulatory lociwere identified under standard and under heat-stress conditions. Afterverification, the causal regulator was identified by screening knock-outmutants of candidate genes. Moreover, lifespan was measured understandard conditions and in strains that received a heat shock treatment.We identified a major stress-related regulatory locus that affects expressionvariation in more than 100 genes and one of the causal genes was found tobe cmk-1. The effects of this variation include modulation of insulin-likesignaling targets supporting a model in which allelic variation in cmk-1regulates a subset of daf-16 targets under stress conditions, leading toincreased stress resistance and prolonged lifespan.In conclusion, genes affecting lifespan variation in nature may not be thoseidentified by mutagenizing a single C. elegans strain. Our data suggests thatpathways previously associated with aging are affected, but not by the usualsuspects.

AB - Genetic control of aging in C. elegans has primarily been studied usingderived mutants of the strain N2. These mutants often display extremelifespan accompanied by increased stress resistance. Yet, identification ofgenes that underlie variation in lifespan and stress tolerance in naturalpopulations remains a major challenge. We investigated gene expressionarchitecture and longevity and found that stress tolerance and lifespan in C.elegans are modulated by natural allelic variation in cmk-1.Variation in gene expression levels was linked to genomic loci (eQTL)using fully sequenced recombinant inbred populations derived fromdivergent wild-type strains N2 and CB4856. In these strains regulatory lociwere identified under standard and under heat-stress conditions. Afterverification, the causal regulator was identified by screening knock-outmutants of candidate genes. Moreover, lifespan was measured understandard conditions and in strains that received a heat shock treatment.We identified a major stress-related regulatory locus that affects expressionvariation in more than 100 genes and one of the causal genes was found tobe cmk-1. The effects of this variation include modulation of insulin-likesignaling targets supporting a model in which allelic variation in cmk-1regulates a subset of daf-16 targets under stress conditions, leading toincreased stress resistance and prolonged lifespan.In conclusion, genes affecting lifespan variation in nature may not be thoseidentified by mutagenizing a single C. elegans strain. Our data suggests thatpathways previously associated with aging are affected, but not by the usualsuspects.

M3 - Poster

ER -

Snoek LB, Sterken MG, Bevers RPJ, Volkers JM, van 't Hof A, Brenchley R et al. Stress tolerance and lifespan in C. elegans are modulated by natural allelic variation in CMK-1. 2016. Poster session presented at Evolutionary Biology of Caenorhabditis and other nematodes, Cold Spring Harbor, United States.