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Hormetins, antioxidants and prooxidants: defining quercetin-, caffeic acid- and rosmarinic acid-mediated life extension in C. elegans

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Abstract

Quercetin, Caffeic- and Rosmarinic acid exposure extend lifespan in Caenorhabditis elegans. This comparative study uncovers basic common and contrasting underlying mechanisms: For all three compounds, life extension was characterized by hormetic dose response curves, but hsp-level expression was variable. Quercetin and Rosmarinic acid both suppressed bacterial growth; however, antibacterial properties were not the dominant reason for life extension. Exposure to Quercetin, Caffeic- and Rosmarinic acid resulted in reduced body size, altered lipid-metabolism and a tendency towards a delay in reproductive timing; however the total number of offspring was not affected. An indirect dietary restriction effect, provoked by either chemo-repulsion or diminished pharyngeal pumping was rejected. Quercetin and Caffeic acid were shown to increase the antioxidative capacity in vivo and, by means of a lipofuscin assay, reduce the oxidative damage in the nematodes. Finally, it was possible to demonstrate that the life and thermotolerance enhancing properties of Caffeic- and Rosmarinic acid both rely on osr-1, sek-1, sir-2.1 and unc-43 plus daf-16 in the case of Caffeic acid. Taken together, hormesis, in vivo antioxidative/prooxidative properties, modulation of genetic players, as well as the re-allocation of energy all contribute (to some extent and dependent on the polyphenol) to life extension.

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References

  • An JH, Blackwell TK (2003) SKN-1 links C. elegans mesodermal specification to conserved oxidative stress response. Genes Dev 17:1882–1893

    Article  PubMed  CAS  Google Scholar 

  • Ashrafi K, Chang FY, Watts JL, Fraser AG, Kamath RS, Ahringer J, Ruvkun G (2003) Genome-wide RNAi analysis of Caenorhabditis elegans fat regulatory genes. Nature 421:268–272

    Article  PubMed  CAS  Google Scholar 

  • Baba S, Osakabe N, Natsume M, Yasuda A, Muto Y, Hiyoshi K, Takano H, Yoshikawa T, Terao J (2005) Absorption, metabolism, degradation and urinary excretion of rosmarinic acid after intake of Perilla frutescens extract in humans. Eur J Nutr 44:1–9

    Article  PubMed  CAS  Google Scholar 

  • Berdichevsky A, Guarente L (2006) A stress response pathway involving sirtuins, forkheads and 14-3-3 proteins. Cell Cycle 5(22):2588–2591

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Berdichevsky A, Nedelcu S, Boulias K, Bishop NA, Guarente L, Horvitz HR (2010) 3-Ketoacyl thiolase delays aging of Caenorhabditis elegans and is required for lifespan extension mediated by sir-2.1. Proc Natl Acad Sci USA 107(44):18927–18932

    Article  PubMed  CAS  Google Scholar 

  • Bligh EG, Dyer WJ (1959) A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37:911–917

    Article  PubMed  CAS  Google Scholar 

  • Bradford MM (1976) Eine schnelle und sensitive Methode zur Quantifizierung von Mikrogramm-Mengen an Protein. Anal Biochem 72:248–254

    Article  PubMed  CAS  Google Scholar 

  • Brenner S (1974) The genetics of Caenorhabditis elegans. Genetics 77:71–94

    PubMed  CAS  Google Scholar 

  • Brunk U, Terman A (2002) Lipofuscin: mechanisms of age-related accumulation and influence on cell function. Free Radic Biol Med 33:611–619

    Article  PubMed  CAS  Google Scholar 

  • Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162(1):156–159

    Article  PubMed  CAS  Google Scholar 

  • Flurkey K, Papaconstantinou J, Miller RA, Harrison DE (2001) Lifespan extension and delayed immune and collagen ageing in mutant mice with defects in growth hormone production. Proc Natl Acad Sci USA 98:6736–6741

    Article  PubMed  CAS  Google Scholar 

  • Garigan D, Hsu AL, Fraser AG, Kamath RS, Ahringer J, Kenyon C (2002) Genetic analysis of tissue ageing in Caenorhabditis elegans: a role for heat-shock factor and bacterial proliferation. Genetics 161:1101–1112

    PubMed  CAS  Google Scholar 

  • Gems D, Riddle DL (2000) Genetic, behavioural and environmental determinants of male longevity in Caenorhabditis elegans. Genetics 154:1597–1610

    PubMed  CAS  Google Scholar 

  • Gruber J, Ng LF, Poovathingal SK, Halliwell B (2009) Deceptively simple but simply deceptive—Caenorhabditis elegans lifespan studies: considerations for aging and antioxidant effects. FEBS Lett 583(21):3377–3387

    Article  PubMed  CAS  Google Scholar 

  • Harman D (1956) Aging: a theory based on free radical and radiation chemistry. J Gerontol 11:298–300

    PubMed  CAS  Google Scholar 

  • Harrington LA, Harley CB (1988) Effect of vitamin E on lifespan and reproduction in Caenorhabditis elegans. Mech Ageing Dev 43:71–78

    Article  PubMed  CAS  Google Scholar 

  • Hosokawa H, Ishii N, Ishida H, Ichimori K, Nakazawa H, Suzuki K (1994) Rapid accumulation of fluorescent material with aging in an oxygen-sensitive mutant mev-1 of Caenorhabditis elegans. Mech Ageing Dev 74:161–170

    Article  PubMed  CAS  Google Scholar 

  • Houthoofd K, Vanfleteren JR (2006) The longevity effect of dietary restriction in Caenorhabditis elegans. Exp Gerontol 41(10):1026–1031

    Article  PubMed  CAS  Google Scholar 

  • Huang C, Xiong C, Kornfeld K (2004) Measurements of age-related changes of physiological processes that predict lifespan of Caenorhabditis elegans. Proc Natl Acad Sci USA 101:8084–8089

    Article  PubMed  CAS  Google Scholar 

  • Ishii N, Fujii M, Hartman PS, Tusda M, Yasuda K, Senoo-Matsuda N, Yanase S, Ayusawa D, Suzuki K (1998) A mutation in succinate dehydrogenase cytochrome b causes oxidative stress and ageing in nematodes. Nature 394:694–697

    Article  PubMed  CAS  Google Scholar 

  • Kaeberlein TL, Smith ED, Tsuchiya M, Welton KL, Thomas JH, Fields S, Kennedy BK, Kaeberlein M (2006) Lifespan extension in Caenorhabditis elegans by complete removal of food. Aging Cell 5:487–494

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Kim DH, Feinbaum R, Alloing G, Emerson FE, Garsin DA, Inoue H, Tanaka-Hino M, Hisamoto N, Matsumoto K, Tan MW, Ausubel FM (2002) A conserved p38 MAP kinase pathway in Caenorhabditis elegans innate immunity. Science 297:623–626

    Article  PubMed  CAS  Google Scholar 

  • Kirkwood TB (1977) Evolution of ageing. Nature 270:301–304

    Article  PubMed  CAS  Google Scholar 

  • Kirkwood TB (1988) The nature and causes of ageing. Ciba Found Symp 134:193–207

    PubMed  CAS  Google Scholar 

  • Konishi Y, Hitomi Y, Yoshida M, Yoshioka E (2005) Pharmacokinetic study of caffeic and rosmarinic acids in rats after oral administration. J Agric Food Chem 53:4740–4746

    Article  PubMed  CAS  Google Scholar 

  • Lafay S, Gil-Izquierdo A (2008) Bioavailability of phenolic acids. Phytochem Rev 7:301–311

    Article  CAS  Google Scholar 

  • Lakowski B, Hekimi S (1998) The genetics of caloric restriction in Caenorhabditis elegans. Proc Natl Acad Sci USA 95:13091–13096

    Article  PubMed  CAS  Google Scholar 

  • Landis JN, Murphy CT (2010) Integration of diverse inputs in the regulation of Caenorhabditis elegans DAF-16/FOXO. Dev Dyn 239:1405–1412

    PubMed  CAS  Google Scholar 

  • Le Bourg E (2009) Hormesis, ageing and longevity. Biochem Biophys Acta 1790(10):1030–1039

    PubMed  CAS  Google Scholar 

  • Lin SJ, Guarente L (2003) Nicotinamide adenine dinucleotide, a metabolic regulator of transcription, longevity and disease. Curr Opin Cell Biol 15:241–246

    Article  PubMed  CAS  Google Scholar 

  • Lin SJ, Defossez PA, Guarente L (2000) Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. Science 289:2126–2128

    Article  PubMed  CAS  Google Scholar 

  • Liu RH (2003) Health benefits of fruits and vegetables are from additive and synergistic combination of phytochemicals. Am J Clin Nutr 78:517–520

    Google Scholar 

  • Liu RH (2004) Potential synergy of phytochemicals in cancer prevention: mechanism of action. J Nutr 134(12 Suppl):3479–3485

    Google Scholar 

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods 25:402–408

    Article  PubMed  CAS  Google Scholar 

  • Makris DP, Rossiter JT (2001) Comparison of quercetin and a nonorthohydroxy flavonol as antioxidants by competing in vitro oxidation reactions. J Agric Food Chem 49:3370–3377

    Article  PubMed  CAS  Google Scholar 

  • Menzel R, Stürzenbaum S, Bärenwaldt A, Kulas J, Steinberg CEW (2005) Humic material induces behavioral and global transcriptional responses in the nematode Caenorhabditis elegans. Environ Sci Technol 39:8324–8332

    Article  PubMed  CAS  Google Scholar 

  • Muller FL, Lustgarten MS, Jang Y, Richardson A, Van Remmen H (2007) Trends in oxidative aging theories. Free Radic Biol Med 43(4):477–503

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Nielsen MD, Luo X, Biteau B, Syverson K, Jasper H (2008) 14-3-3 Epsilon antagonizes FoxO to control growth, apoptosis and longevity in Drosophila. Aging Cell 7:688–699

    Article  PubMed  CAS  Google Scholar 

  • North BJ, Verdin E (2004) Sirtuins: Sir2-related NAD-dependent protein deacetylases. Genome Biol 5:224

    Article  PubMed  Google Scholar 

  • O’Rourke EJ, Soukas AA, Carr CE, Ruvkun G (2009) C. elegans major fats are stored in vesicles distinct from lysosome-related organelles. Cell Metab 10(5):430–435

    Article  PubMed  Google Scholar 

  • Ogata T, Manabe S (1990) Correlation between lipid peroxidation and morphological manifestation of paraquat-induced lung injury in rats. Arch Toxicol 64(1):7–13

    Google Scholar 

  • Partridge L, Gems D (2007) Benchmarks for ageing studies. Nature 450(7167):165–167

    Article  PubMed  CAS  Google Scholar 

  • Pietsch K, Saul N, Menzel R, Stürzenbaum S, Steinberg CEW (2009) Quercetin mediated lifespan extension in Caenorhabditis elegans is modulated by age-1, daf-2, sek-1, and unc-43. Biogerontology 10(5):565–578

    Article  PubMed  CAS  Google Scholar 

  • Pietsch K, Hofmann S, Henkel R, Saul N, Menzel R, Steinberg CEW (2010) The plant polyphenol caffeic acid affects life traits differently in the nematode Caenorhabditis elegans and the cladoceran Moina macrocopa. Fresenius Environ Bull 19:1238–1244

    CAS  Google Scholar 

  • Popov I, Lewin G (1999) Antioxidative homeostasis: characterization by means of chemiluminescent technique. Methods Enzymol 300:437–456

    Article  PubMed  CAS  Google Scholar 

  • Pun PB, Gruber J, Tang SY, Schaffer S, Ong RL, Fong S, Ng LF, Cheah I, Halliwell B (2010) Ageing in nematodes: do antioxidants extend lifespan in Caenorhabditis elegans? Biogerontology 11(1):17–30

    Article  PubMed  Google Scholar 

  • Rattan SI (2006) Theories of biological aging: genes, proteins, and free radicals. Free Radic Res 40(12):1230–1238

    Article  PubMed  CAS  Google Scholar 

  • Rattan SI (2008) Hormesis in aging. Ageing Res Rev 7(1):63–78

    Article  PubMed  Google Scholar 

  • Reiner DJ, Newton EM, Tian H, Thomas JH (1999) Diverse behavioural defects caused by mutations in Caenorhabditis elegans unc-43 CaM kinase II. Nature 402:199–203

    Article  PubMed  CAS  Google Scholar 

  • Rogina B, Helfand SL (2004) Sir2 mediates longevity in the fly through a pathway related to calorie restriction. Proc Natl Acad Sci USA 101:15998–16003

    Article  PubMed  CAS  Google Scholar 

  • Sagasti A, Hisamoto N, Hyodo J, Tanaka-Hino M, Matsumoto K, Bargmann CI (2001) The CaMKII UNC-43 activates the MAPKKK NSY-1 to execute a lateral signaling decision required for asymmetric olfactory neuron fates. Cell 105(2):221–232

    Article  PubMed  CAS  Google Scholar 

  • Saul N, Pietsch K, Menzel R, Steinberg CEW (2008) Quercetin-mediated longevity in Caenorhabditis elegans: Is DAF-16 involved? Mech Ageing Dev 129:611–613

    Article  PubMed  CAS  Google Scholar 

  • Saul N, Pietsch K, Menzel R, Stürzenbaum SR, Steinberg CEW (2009) Catechin induced longevity in C. elegans: from key regulator genes to disposable soma. Mech Ageing Dev 130(8):477–486

    Article  PubMed  CAS  Google Scholar 

  • Saul N, Pietsch K, Menzel R, Stürzenbaum SR, Steinberg CEW (2010) The longevity effect of tannic acid in Caenorhabditis elegans: disposable soma meets hormesis. J Gerontol A Biol Sci Med Sci 65(6):626–635

    Article  PubMed  Google Scholar 

  • Smith P, Heath D (1976) Paraquat. CRC Crit Rev Toxicol 4:411–445

    PubMed  CAS  Google Scholar 

  • Solomon A, Bandhakavi S, Jabbar S, Shah R, Beitel GJ, Morimoto RI (2004) Caenorhabditis elegans OSR-1 regulates behavioral and physiological responses to hyperosmotic environments. Genetics 167:161–170

    Article  PubMed  CAS  Google Scholar 

  • Steinberg CEW, Ouerghemmi N, Herrmann S, Bouchnak R, Timofeyev MA, Menzel R (2010) Stress by poor food quality and exposure to humic substances: Daphnia magna responds with oxidative stress, lifespan extension, but reduced offspring numbers. Hydrobiologia 652:223–236

    Article  CAS  Google Scholar 

  • Strange K, Christensen M, Morrison R (2007) Primary culture of Caenorhabditis elegans developing embryo cells for electrophysiological, cell biological and molecular studies. Nat Protoc 2(4):1003–1012

    Article  PubMed  CAS  Google Scholar 

  • Szewczyk NJ, Udranszky IA, Kozak E, Sunga J, Kim SK, Jacobson LA, Conley CA (2006) Delayed development and lifespan extension as features of metabolic lifestyle alteration in C elegans under dietary restriction. J Exp Biol 209(20):4129–4139

    Article  PubMed  CAS  Google Scholar 

  • Tatar M, Bartke A, Antebi A (2003) The endocrine regulation of ageing by insulin-like signals. Science 299:1346–1351

    Article  PubMed  CAS  Google Scholar 

  • Tissenbaum HA, Guarente L (2001) Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature 410:227–230

    Article  PubMed  CAS  Google Scholar 

  • Urano F, Calfon M, Yoneda T, Yun C, Kiraly M, Clark SG, Ron D (2002) A survival pathway for Caenorhabditis elegans with a blocked unfolded protein response. J Cell Biol 158:639–646

    Article  PubMed  CAS  Google Scholar 

  • Viswanathan M, Kim SK, Berdichevsky A, Guarente L (2005) A role for SIR-2.1 regulation of ER stress response genes in determining C. elegans lifespan. Dev Cell 5:605–615

    Article  Google Scholar 

  • Wang Y, Tissenbaum HA (2006) Overlapping and distinct functions for a Caenorhabditis elegans SIR2 and DAF-16/FOXO. Mech Ageing Dev 127:48–56

    Article  PubMed  CAS  Google Scholar 

  • Wilson MA, Shukitt-Hale B, Kalt W, Ingram DK, Joseph JA, Wolkow CA (2006) Blueberry polyphenols increase lifespan and thermotolerance in Caenorhabditis elegans. Aging Cell 5:59–68

    Article  PubMed  CAS  Google Scholar 

  • Wood JG, Rogina B, Lavu S, Howitz K, Helfand SL, Tatar M, Sinclair D (2004) Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature 430:686–689

    Article  PubMed  CAS  Google Scholar 

  • 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 Age Dev 123:1579–1587

    Article  CAS  Google Scholar 

  • Yasaka T, Okudaira K, Fujito H, Matsumoto J, Ohya I, Miyamoto Y (1986) Further studies of lipid peroxidation in human paraquat poisoning. Arch Intern Med 146:681–685

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was partially supported by a grants (STE 673/16-1, STE 673/18-1) awarded by the German Research Foundation (DFG) and by the Biotechnology and Biological Sciences Research Council (BBSRC grant BB/E025099 and a BBSRC Underwood Fellowship). Furthermore, we thank the Caenorhabditis Genetics Centre, which is funded by the National Institutes of Health National Centre for Research Resources, for the supply of the Caenorhabditis elegans strains.

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  1. Humboldt-Universität zu Berlin, Department of Biology, Laboratory of Freshwater & Stress Ecology, Späthstr. 80/81, 12437, Berlin, Germany

    Kerstin Pietsch, Nadine Saul, Shumon Chakrabarti, Ralph Menzel & Christian E. W. Steinberg

  2. School of Biomedical & Health Sciences, Analytical and Environmental Science Division, King′s College London, 150 Stamford Street, London, SE1 9NH, UK

    Stephen R. Stürzenbaum

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  1. Kerstin Pietsch
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  2. Nadine Saul
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Correspondence to Kerstin Pietsch.

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Pietsch, K., Saul, N., Chakrabarti, S. et al. Hormetins, antioxidants and prooxidants: defining quercetin-, caffeic acid- and rosmarinic acid-mediated life extension in C. elegans . Biogerontology 12, 329–347 (2011). https://doi.org/10.1007/s10522-011-9334-7

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