Biogerontology

, Volume 12, Issue 4, pp 329–347 | Cite as

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

  • Kerstin Pietsch
  • Nadine Saul
  • Shumon Chakrabarti
  • Stephen R. Stürzenbaum
  • Ralph Menzel
  • Christian E. W. Steinberg
Research Article

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.

Keywords

Hormetin Antioxidant Quercetin Caffeic acid Rosmarinic acid Longevity Caenorhabditis elegans 

Notes

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.

Supplementary material

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References

  1. An JH, Blackwell TK (2003) SKN-1 links C. elegans mesodermal specification to conserved oxidative stress response. Genes Dev 17:1882–1893PubMedCrossRefGoogle Scholar
  2. 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 421:268–272PubMedCrossRefGoogle Scholar
  3. 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 44:1–9PubMedCrossRefGoogle Scholar
  4. Berdichevsky A, Guarente L (2006) A stress response pathway involving sirtuins, forkheads and 14-3-3 proteins. Cell Cycle 5(22):2588–2591PubMedCrossRefGoogle Scholar
  5. 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 125:1165–1177PubMedCrossRefGoogle Scholar
  6. 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):18927–18932PubMedCrossRefGoogle Scholar
  7. Bligh EG, Dyer WJ (1959) A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37:911–917PubMedCrossRefGoogle Scholar
  8. Bradford MM (1976) Eine schnelle und sensitive Methode zur Quantifizierung von Mikrogramm-Mengen an Protein. Anal Biochem 72:248–254PubMedCrossRefGoogle Scholar
  9. Brenner S (1974) The genetics of Caenorhabditis elegans. Genetics 77:71–94PubMedGoogle Scholar
  10. Brunk U, Terman A (2002) Lipofuscin: mechanisms of age-related accumulation and influence on cell function. Free Radic Biol Med 33:611–619PubMedCrossRefGoogle Scholar
  11. Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162(1):156–159PubMedCrossRefGoogle Scholar
  12. 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 98:6736–6741PubMedCrossRefGoogle Scholar
  13. 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 161:1101–1112PubMedGoogle Scholar
  14. Gems D, Riddle DL (2000) Genetic, behavioural and environmental determinants of male longevity in Caenorhabditis elegans. Genetics 154:1597–1610PubMedGoogle Scholar
  15. 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):3377–3387PubMedCrossRefGoogle Scholar
  16. Harman D (1956) Aging: a theory based on free radical and radiation chemistry. J Gerontol 11:298–300PubMedGoogle Scholar
  17. Harrington LA, Harley CB (1988) Effect of vitamin E on lifespan and reproduction in Caenorhabditis elegans. Mech Ageing Dev 43:71–78PubMedCrossRefGoogle Scholar
  18. 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 74:161–170PubMedCrossRefGoogle Scholar
  19. Houthoofd K, Vanfleteren JR (2006) The longevity effect of dietary restriction in Caenorhabditis elegans. Exp Gerontol 41(10):1026–1031PubMedCrossRefGoogle Scholar
  20. 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 101:8084–8089PubMedCrossRefGoogle Scholar
  21. 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 394:694–697PubMedCrossRefGoogle Scholar
  22. 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 5:487–494PubMedCrossRefGoogle Scholar
  23. Kenyon C, Chang J, Gensch E, Rudner A, Tabtiang R (1993) A C. elegans mutant that lives twice as long as wild type. Nature 366:461–464PubMedCrossRefGoogle Scholar
  24. 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 297:623–626PubMedCrossRefGoogle Scholar
  25. Kirkwood TB (1977) Evolution of ageing. Nature 270:301–304PubMedCrossRefGoogle Scholar
  26. Kirkwood TB (1988) The nature and causes of ageing. Ciba Found Symp 134:193–207PubMedGoogle Scholar
  27. 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 53:4740–4746PubMedCrossRefGoogle Scholar
  28. Lafay S, Gil-Izquierdo A (2008) Bioavailability of phenolic acids. Phytochem Rev 7:301–311CrossRefGoogle Scholar
  29. Lakowski B, Hekimi S (1998) The genetics of caloric restriction in Caenorhabditis elegans. Proc Natl Acad Sci USA 95:13091–13096PubMedCrossRefGoogle Scholar
  30. Landis JN, Murphy CT (2010) Integration of diverse inputs in the regulation of Caenorhabditis elegans DAF-16/FOXO. Dev Dyn 239:1405–1412PubMedGoogle Scholar
  31. Le Bourg E (2009) Hormesis, ageing and longevity. Biochem Biophys Acta 1790(10):1030–1039PubMedGoogle Scholar
  32. Lin SJ, Guarente L (2003) Nicotinamide adenine dinucleotide, a metabolic regulator of transcription, longevity and disease. Curr Opin Cell Biol 15:241–246PubMedCrossRefGoogle Scholar
  33. Lin SJ, Defossez PA, Guarente L (2000) Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. Science 289:2126–2128PubMedCrossRefGoogle Scholar
  34. Liu RH (2003) Health benefits of fruits and vegetables are from additive and synergistic combination of phytochemicals. Am J Clin Nutr 78:517–520Google Scholar
  35. Liu RH (2004) Potential synergy of phytochemicals in cancer prevention: mechanism of action. J Nutr 134(12 Suppl):3479–3485Google Scholar
  36. 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 25:402–408PubMedCrossRefGoogle Scholar
  37. Makris DP, Rossiter JT (2001) Comparison of quercetin and a nonorthohydroxy flavonol as antioxidants by competing in vitro oxidation reactions. J Agric Food Chem 49:3370–3377PubMedCrossRefGoogle Scholar
  38. 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 39:8324–8332PubMedCrossRefGoogle Scholar
  39. Muller FL, Lustgarten MS, Jang Y, Richardson A, Van Remmen H (2007) Trends in oxidative aging theories. Free Radic Biol Med 43(4):477–503PubMedCrossRefGoogle Scholar
  40. 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 424:277–283PubMedCrossRefGoogle Scholar
  41. 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 7:688–699PubMedCrossRefGoogle Scholar
  42. North BJ, Verdin E (2004) Sirtuins: Sir2-related NAD-dependent protein deacetylases. Genome Biol 5:224PubMedCrossRefGoogle Scholar
  43. 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):430–435PubMedCrossRefGoogle Scholar
  44. Ogata T, Manabe S (1990) Correlation between lipid peroxidation and morphological manifestation of paraquat-induced lung injury in rats. Arch Toxicol 64(1):7–13Google Scholar
  45. Partridge L, Gems D (2007) Benchmarks for ageing studies. Nature 450(7167):165–167PubMedCrossRefGoogle Scholar
  46. 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):565–578PubMedCrossRefGoogle Scholar
  47. 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 19:1238–1244Google Scholar
  48. Popov I, Lewin G (1999) Antioxidative homeostasis: characterization by means of chemiluminescent technique. Methods Enzymol 300:437–456PubMedCrossRefGoogle Scholar
  49. 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):17–30PubMedCrossRefGoogle Scholar
  50. Rattan SI (2006) Theories of biological aging: genes, proteins, and free radicals. Free Radic Res 40(12):1230–1238PubMedCrossRefGoogle Scholar
  51. Rattan SI (2008) Hormesis in aging. Ageing Res Rev 7(1):63–78PubMedCrossRefGoogle Scholar
  52. Reiner DJ, Newton EM, Tian H, Thomas JH (1999) Diverse behavioural defects caused by mutations in Caenorhabditis elegans unc-43 CaM kinase II. Nature 402:199–203PubMedCrossRefGoogle Scholar
  53. Rogina B, Helfand SL (2004) Sir2 mediates longevity in the fly through a pathway related to calorie restriction. Proc Natl Acad Sci USA 101:15998–16003PubMedCrossRefGoogle Scholar
  54. 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):221–232PubMedCrossRefGoogle Scholar
  55. Saul N, Pietsch K, Menzel R, Steinberg CEW (2008) Quercetin-mediated longevity in Caenorhabditis elegans: Is DAF-16 involved? Mech Ageing Dev 129:611–613PubMedCrossRefGoogle Scholar
  56. 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):477–486PubMedCrossRefGoogle Scholar
  57. 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):626–635PubMedCrossRefGoogle Scholar
  58. Smith P, Heath D (1976) Paraquat. CRC Crit Rev Toxicol 4:411–445PubMedGoogle Scholar
  59. 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 167:161–170PubMedCrossRefGoogle Scholar
  60. 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 652:223–236CrossRefGoogle Scholar
  61. 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):1003–1012PubMedCrossRefGoogle Scholar
  62. 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):4129–4139PubMedCrossRefGoogle Scholar
  63. Tatar M, Bartke A, Antebi A (2003) The endocrine regulation of ageing by insulin-like signals. Science 299:1346–1351PubMedCrossRefGoogle Scholar
  64. Tissenbaum HA, Guarente L (2001) Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature 410:227–230PubMedCrossRefGoogle Scholar
  65. 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 158:639–646PubMedCrossRefGoogle Scholar
  66. 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 5:605–615CrossRefGoogle Scholar
  67. Wang Y, Tissenbaum HA (2006) Overlapping and distinct functions for a Caenorhabditis elegans SIR2 and DAF-16/FOXO. Mech Ageing Dev 127:48–56PubMedCrossRefGoogle Scholar
  68. 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 5:59–68PubMedCrossRefGoogle Scholar
  69. 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 430:686–689PubMedCrossRefGoogle Scholar
  70. 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 123:1579–1587CrossRefGoogle Scholar
  71. 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 146:681–685PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Kerstin Pietsch
    • 1
  • Nadine Saul
    • 1
  • Shumon Chakrabarti
    • 1
  • Stephen R. Stürzenbaum
    • 2
  • Ralph Menzel
    • 1
  • Christian E. W. Steinberg
    • 1
  1. 1.Humboldt-Universität zu BerlinDepartment of Biology, Laboratory of Freshwater & Stress EcologyBerlinGermany
  2. 2.School of Biomedical & Health Sciences, Analytical and Environmental Science DivisionKing′s College LondonLondonUK

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