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

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

Research output: Chapter in Book/Report/Conference proceedingAbstract

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
Title of host publicationProceedings of Molecular Biology of Ageing 2015
Pages134-134
Publication statusPublished - 2015
EventMolecular Biology of Ageing 2015, Groningen, The Netherlands -
Duration: 25 Oct 201528 Oct 2015

Conference

ConferenceMolecular Biology of Ageing 2015, Groningen, The Netherlands
Period25/10/1528/10/15

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

Cite this

Sterken, M. G., Snoek, L. B., Bevers, R. P. J., Volkers, R. J. M., van 't Hof, A., Brenchley, R., ... Kammenga, J. E. (2015). Stress tolerance and lifespan in C. elegans are modulated by natural allelic variation in cmk-1. In Proceedings of Molecular Biology of Ageing 2015 (pp. 134-134)
Sterken, M.G. ; Snoek, L.B. ; Bevers, R.P.J. ; Volkers, R.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. Proceedings of Molecular Biology of Ageing 2015. 2015. pp. 134-134
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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.",
author = "M.G. Sterken and L.B. Snoek and R.P.J. Bevers and R.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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Sterken, MG, Snoek, LB, Bevers, RPJ, Volkers, RJM, van 't Hof, A, Brenchley, R, Lehner, B, Cossins, A & Kammenga, JE 2015, Stress tolerance and lifespan in C. elegans are modulated by natural allelic variation in cmk-1. in Proceedings of Molecular Biology of Ageing 2015. pp. 134-134, Molecular Biology of Ageing 2015, Groningen, The Netherlands, 25/10/15.

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

Proceedings of Molecular Biology of Ageing 2015. 2015. p. 134-134.

Research output: Chapter in Book/Report/Conference proceedingAbstract

TY - CHAP

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

AU - Sterken, M.G.

AU - Snoek, L.B.

AU - Bevers, R.P.J.

AU - Volkers, R.J.M.

AU - van 't Hof, A.

AU - Brenchley, R.

AU - Lehner, B.

AU - Cossins, A.

AU - Kammenga, J.E.

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

M3 - Abstract

SP - 134

EP - 134

BT - Proceedings of Molecular Biology of Ageing 2015

ER -

Sterken MG, Snoek LB, Bevers RPJ, Volkers RJM, van 't Hof A, Brenchley R et al. Stress tolerance and lifespan in C. elegans are modulated by natural allelic variation in cmk-1. In Proceedings of Molecular Biology of Ageing 2015. 2015. p. 134-134