Abstract
In Caenorhabditis elegans pretreatment with juglone, a generator of reactive oxygen species (ROS) provides a subsequently increased ROS-resistance. We investigated whether juglone at low or high concentrations when provided via the oral route in a liquid axenic medium affects normal lifespan of C. elegans. High juglone concentrations led to premature death, low concentrations were tolerated well and caused a prolongation of lifespan. Lifespan extension under moderate oxidative stress was associated with increased expression of small heat-shock protein HSP-16.2, enhanced glutathione levels, and nuclear translocation of DAF-16. Silencing or deletion of DAF-16 prevented the juglone-induced adaptations. RNA-interference for SIR-2.1 had the same effects as the deletion of DAF-16 but did not affect nuclear accumulation of DAF-16. Our studies demonstrate that DAF-16- and SIR-2.1-dependent alterations in gene expression after a ROS challenge lead to a lifespan extension in C. elegans as long as the stressor concentration does not exceed the saturable protective capacity.
Similar content being viewed by others
References
Aebi H (1986) Catalase in vitro. Methods Enzymol 105:121–126. doi:10.1016/S0076-6879(84)05016-3
Berdichevsky A, Guarente L (2006) A stress response pathway involving sirtuins, forkheads and 14–3-3 proteins. Cell Cycle 5:2588–2591
Berdichevsky A, Viswanathan M, Horvitz HR, Guarente L (2006) C. elegans SIR-2.1 interacts with 14-3-3 proteins to activate DAF-16 and extend lifespan. Cell 125:1165–1177. doi:10.1016/j.cell.2006.04.036
Blum J, Fridovich I (1983) Superoxide, hydrogen peroxide, and oxygen toxicity in two free-living nematode species. Arch Biochem Biophys 222:35–43. doi:10.1016/0003-9861(83)90499-X
Brenner S (1974) The genetics of Caenorhabditis elegans. Genetics 77:71–94
Brunet A, Sweeney LB, Sturgill JF, Chua KF, Greer PL, Lin Y, Tran H, Ross SE, Mostoslavsky R, Cohen HY, Hu LS, Cheng HL, Jedrychowski MP, Gygi SP, Sinclair DA, Alt FW, Greenberg ME (2004) Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science 303:2011–2015. doi:10.1126/science.1094637
Calabrese EJ, Baldwin LA, Holland CD (1999) Hormesis: a highly generalizable and reproducible phenomenon with important implications for risk assessment. Risk Anal 19:261–281
Cypser JR, Johnson TE (2002) Multiple stressors in Caenorhabditis elegans induce stress hormesis and extended longevity. J Gerontol A Biol Sci Med Sci 57:B109–B114
de Castro E, Hegi de Castro S, Johnson TE (2004) Isolation of long-lived mutants in Caenorhabditis elegans using selection for resistance to juglone. Free Radic Biol Med 37:139–145. doi:10.1016/j.freeradbiomed.2004.04.021
Doonan R, McElwee JJ, Matthijssens F, Walker GA, Houthoofd K, Back P, Matscheski A, Vanfleteren JR, Gems D (2008) Against the oxidative damage theory of aging: superoxide dismutases protect against oxidative stress but have little or no effect on life span in Caenorhabditis elegans. Genes Dev 22:3236–3241. doi:10.1101/gad.504808
Frescas D, Valenti L, Accili D (2005) Nuclear trapping of the forkhead transcription factor FoxO1 via Sirt-dependent deacetylation promotes expression of glucogenetic genes. J Biol Chem 280:20589–20595. doi:10.1074/jbc.M412357200
Geanacopoulos M (2004) The determinants of lifespan in the nematode Caenorhabditis elegans: a short primer. Sci Prog 87:227–247. doi:10.3184/003685004783238472
Harman D (1972) Free radical theory of aging: dietary implications. Am J Clin Nutr 25:839–843
Hekimi S, Guarente L (2003) Genetics and the specificity of the aging process. Science 299:1351–1354. doi:10.1126/science.1082358
Henderson ST, Johnson TE (2001) daf-16 integrates development and environmental inputs to mediate aging in the nematode Caenorhabditis elegans. Curr Biol 11:1975–1980. doi:10.1016/S0960-9822(01)00594-2
Hsu AL, Murphy CT, Kenyon C (2003) Regulation of aging and age-related disease by DAF-16 and heat-shock factor. Science 300:1142–1145. doi:10.1126/science.1083701
Kamath RS, Martinez-Campos M, Zipperlen P, Fraser AG, Ahringer J (2001) Effectiveness of specific RNA-mediated interference through ingested double-stranded RNA in Caenorhabditis elegans. Genome Biol 2:RESEARCH0002
Kenyon C, Chang J, Gensch E, Rudner A, Tabtiang R (1993) A C. elegans mutant that lives twice as long as wild type. Nature 366:461–464. doi:10.1038/366461a0
Lamitina ST, Strange K (2005) Transcriptional targets of DAF-16 insulin signalling pathway protect C. elegans from extreme hypertonic stress. Am J Physiol Cell Physiol 288:C467–C474. doi:10.1152/ajpcell.00451.2004
LaPenotiere HF, French DY, Szilagyi M, Clegg ED (2001) A skim milk-supplemented axenic medium to support development and reproduction of C. elegans. Worm Breed Gaz 17
Larsen PL, Albert PS, Riddle DL (1995) Genes that regulate both development and longevity in Caenorhabditis elegans. Genetics 139:1567–1583
Lin K, Dorman JB, Rodan A, Kenyon C (1997) Daf-16: an HNF-3/forkhead family member that can function to double the lifespan of Caenorhabditis elegans. Science 278:1319–1322. doi:10.1126/science.278.5341.1319
Lithgow GJ, White TM, Melov S, Johnson TE (1995) Thermotolerance and extended lifespan conferred by single-gene mutations and induced by thermal stress. Proc Natl Acad Sci USA 92:7540–7544. doi:10.1073/pnas.92.16.7540
Luo Y (2004) Long-lived worms and aging. Redox Rep 9:65–69. doi:10.1179/135100004225004733
Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47:469–474. doi:10.1111/j.1432-1033.1974.tb03714.x
Masse I, Molin L, Mouchiroud L, Vanhems P, Palladino F, Billaud M, Solari F (2008) A novel role for the SMG-1 kinase in lifespan and oxidative stress resistance in Caenorhabditis elegans. PLoS ONE 3:e3354. doi:10.1371/journal.pone.0003354
Mehlen P, Kretz-Remy C, Preville X, Arrigo AP (1996) Human Hsp27, Drosophila Hsp27 and human alpha B-crystallin expression-mediated increase in glutathione is essential for the protective activity of these proteins against TNFalpha-induced cell death. EMBO J 15:2695–2706
Motta MC, Divecha N, Lemieux M, Kamel C, Chen D, Gu W, Bultsma Y, McBurney M, Guarente L (2004) Mammalian SIRT1 represses forkhead transcription factors. Cell 116:551–563. doi:10.1016/S0092-8674(04)00126-6
Murphy CT (2006) The search for DAF-16/FOXO transcriptional targets: approaches and discoveries. Exp Gerontol 41:910–921. doi:10.1016/j.exger.2006.06.040
Murphy CT, McCarroll SA, Bargmann CI, Fraser A, Kamath RS, Ahringer J, Li H, Kenyon C (2003) Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature 424:277–283. doi:10.1038/nature01789
Oh SW, Mukhopadhyay A, Svrzikapa N, Jiang F, Davis RJ, Tissenbaum HA (2005) JNK regulates lifespan in Caenorhabditis elegans by modulating nuclear translocation of forkhead transcription factor/DAF-16. Proc Natl Acad Sci USA 102:4494–4499. doi:10.1073/pnas.0500749102
Petriv OI, Rachubinski RA (2004) Lack of peroxisomal catalase causes a progeric phenotype in Caenorhabditis elegans. J Biol Chem 279:19996–20001. doi:10.1074/jbc.M400207200
Preville X, Salvemini F, Giraud S, Chaufour S, Paul C, Stepien G, Ursini MV, Arrigo AP (1999) Mammalian small stress proteins protect against oxidative stress through their ability to increase glucose-6-phosphate dehydrogenase activity and by maintaining optimal cellular detoxifying machinery. Exp Cell Res 247:61–78. doi:10.1006/excr.1998.4347
Rahman I, Kode A, Biswas SK (2006) Assay for quantitative determination of glutathione and glutathione disulfide levels using enzymatic recycling method. Nat Protocols 1:3159–3165. doi:10.1038/nprot.2006.378
Rea SL, Wu D, Cypser JR, Vaupel JW, Johnson TE (2005) A stress-sensitive reporter predicts longevity in isogenic populations of Caenorhabditis elegans. Nat Genet 37:894–898. doi:10.1038/ng1608
Sonneborn JS (2005) The myth and reality of reversal of aging by hormesis. Ann N Y Acad Sci 1057:165–176. doi:10.1196/annals.1356.010
Stiernagel T (1999) Maintenance of C. elegans. In: Hope IA (ed) C. elegans: a practical approach. Oxford, Oxford University press, pp. xxi, 281
Tissenbaum HA, Guarente L (2001) Increased dosage of a SIR-2 gene extends lifespan in Caenorhabditis elegans. Nature 410:227–230. doi:10.1038/35065638
Van Raamsdonk JM, Hekimi S (2009) Deletion of the mitochondrial superoxide dismutase sod-2 extends lifespan in Caenorhabditis elegans. PLoS Genet 5:e1000361. doi:10.1371/journal.pgen.1000361
Walker GA, Lithgow GJ (2003) Lifespan extension in C. elegans by a molecular chaperone dependent upon insulin-like signals. Aging Cell 2:131–139. doi:10.1046/j.1474-9728.2003.00045.x
Wang Y, Tissenbaum HA (2006) Overlapping and distinct functions for a Caenorhabditis elegans SIR2 and DAF-16/FOXO. Mech Ageing Dev 127:48–56. doi:10.1016/j.mad.2005.09.005
Wang Y, Oh SW, Deplancke B, Luo J, Walhout AJ, Tissenbaum HA (2006) C. elegans 14–3-3 proteins regulate life span and interact with SIR-2.1 and DAF-16/FOXO. Mech Ageing Dev 127:741–747. doi:10.1016/j.mad.2006.05.005
Yanase S, Hartman PS, Ito A, Ishii N (1999) Oxidative stress pretreatment increases the X-radiation resistance of the nematode Caenorhabditis elegans. Mutat Res 426:31–39. doi:10.1016/S0027-5107(99)00079-2
Yanase S, Yasuda K, Ishii N (2002) Adaptive responses to oxidative damage in three mutants of Caenorhabditis elegans (age-1, mev-1 and daf-16) that affect lifespan. Mech Ageing Dev 123:1579–1587. doi:10.1016/S0047-6374(02)00093-3
Zarse K, Schulz TJ, Birringer M, Ristow M (2007) Impaired respiration is positively correlated with decreased life span in Caenorhabditis elegans models of Friedreich Ataxia. FASEB J 21:1271–1275. doi:10.1096/fj.06-6994com
Acknowledgments
We thank the Caenorhabditis Genetics Center, University of Minnesota for supplying the Bristol N2, CL2070, CF1038, CF1553, TJ356, and CB1370 strains. We acknowledge Mr. A. Stamfort for statistical advice.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Heidler, T., Hartwig, K., Daniel, H. et al. Caenorhabditiselegans lifespan extension caused by treatment with an orally active ROS-generator is dependent on DAF-16 and SIR-2.1. Biogerontology 11, 183–195 (2010). https://doi.org/10.1007/s10522-009-9239-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10522-009-9239-x