Biogerontology

, Volume 14, Issue 1, pp 73–87

Mechanism underlying prolongevity induced by bifidobacteria in Caenorhabditis elegans

  • Tomomi Komura
  • Takanori Ikeda
  • Chikako Yasui
  • Shigeru Saeki
  • Yoshikazu Nishikawa
Research Article

Abstract

Lactobacilli and bifidobacteria are probiotic bacteria that modify host defense systems and have the ability to extend the lifespan of the nematode Caenorhabditis elegans. Here, we attempted to elucidate the mechanism by which bifidobacteria prolong the lifespan of C. elegans. When the nematode was fed Bifidobacterium infantis (BI) mixed at various ratios with the standard food bacterium Escherichia coli strain OP50 (OP), the mean lifespan of worms was extended in a dose-dependent manner. Worms fed BI displayed higher locomotion and produced more offspring than control worms. The growth curves of nematodes were similar regardless of the amount of BI mixed with OP, suggesting that BI did not induce prolongevity effects through caloric restriction. Notably, feeding worms the cell wall fraction of BI alone was sufficient to promote prolongevity. The accumulation of protein carbonyls and lipofuscin, a biochemical marker of aging, was also lower in worms fed BI; however, the worms displayed similar susceptibility to heat, hydrogen peroxide, and paraquat, an inducer of free radicals, as the control worms. As a result of BI feeding, loss-of-function mutants of daf-16, jnk-1, aak-2, tol-1, and tir-1 exhibited a longer lifespan than OP-fed control worms, but BI failed to extend the lifespan of pmk-1, skn-1, and vhp-1 mutants. As skn-1 induces phase 2 detoxification enzymes, our findings suggest that cell wall components of bifidobacteria increase the average lifespan of C. elegans via activation of skn-1, regulated by the p38 MAPK pathway, but not by general activation of the host defense system via DAF-16.

Keywords

Longevity Nematodes Probiotics Aging Innate immunity 

Supplementary material

10522_2012_9411_MOESM1_ESM.docx (49 kb)
Supplementary material 1 (DOCX 50 kb)

References

  1. Anyanful A, Dolan-Livengood JM, Lewis T, Sheth S, Dezalia MN, Sherman MA, Kalman LV, Benian GM, Kalman D (2005) Paralysis and killing of Caenorhabditis elegans by enteropathogenic Escherichia coli requires the bacterial tryptophanase gene. Mol Microbiol 57:988–1007PubMedCrossRefGoogle Scholar
  2. Apfeld J, O’Connor G, McDonagh T, DiStefano PS, Curtis R (2004) The AMP-activated protein kinase AAK-2 links energy levels and insulin-like signals to lifespan in C. elegans. Genes Dev 18:3004–3009PubMedCrossRefGoogle Scholar
  3. Austad SN (2012) AGEING Mixed results for dieting monkeys. Nature 489:210–211PubMedGoogle Scholar
  4. Bishop NA, Guarente L (2007) Two neurons mediate diet-restriction-induced longevity in C. elegans. Nature 447:545–549PubMedCrossRefGoogle Scholar
  5. Bogden JD, Louria DB (2004) Nutrition and immunity in the elderly. In: Bendich A, Hughes DA, Gail Darlington J (eds) Diet and human immune function. Humana Press, Totowa, pp 79–101CrossRefGoogle Scholar
  6. Bradley SF, Kauffman CA (1990) Aging and the response to salmonella infection. Exp Gerontol 25:75–80PubMedCrossRefGoogle Scholar
  7. Cannizzo ES, Clement CC, Sahu R, Follo C, Santambrogio L (2011) Oxidative stress, inflamm-aging and immunosenescence. J Proteomics 74:2313–2323PubMedCrossRefGoogle Scholar
  8. Effros RB, Walford RL, Weindruch R, Mitcheltree C (1991) Influences of dietary restriction on immunity to influenza in aged mice. J Gerontol 46:B142–B147PubMedCrossRefGoogle Scholar
  9. Finch CE, Ruvkun G (2001) The genetics of aging. Annu Rev Genomics Hum Genet 2:435–462PubMedCrossRefGoogle Scholar
  10. Fulop T, Larbi A, Hirokawa K, Mocchegiani E, Lesourd B, Castle S, Wikby A, Franceschi C, Pawelec G (2007) Immunosupportive therapies in aging. Clin Intervent Aging 2:33–54CrossRefGoogle Scholar
  11. Garigan D, Hsu AL, Fraser AG, Kamath RS, Ahringer J, Kenyon C (2002) Genetic analysis of tissue aging in Caenorhabditis elegans: a role for heat-shock factor and bacterial proliferation. Genetics 161:1101–1112PubMedGoogle Scholar
  12. Gregersen T (1978) Rapid method for distinction of gram-negative from gram-positive bacteria. Eur J Appl Microbiol Biotechnol 5:123–127CrossRefGoogle Scholar
  13. Grubeck-Loebenstein B (1997) Changes in the aging immune system. Biologicals 25:205–208PubMedCrossRefGoogle Scholar
  14. Gruber J, Ng LF, Fong S, Wong YT, Koh SA, Chen CB, Shui G, Cheong WF, Schaffer S, Wenk MR, Halliwell B (2011) Mitochondrial changes in ageing Caenorhabditis elegans—what do we learn from superoxide dismutase knockouts? Plos one 6:e19444PubMedCrossRefGoogle Scholar
  15. Guarente L (2008) Mitochondria–a nexus for aging, calorie restriction, and sirtuins? Cell 132:171–176PubMedCrossRefGoogle Scholar
  16. Hayek MG, Taylor SF, Bender BS, Han SN, Meydani M, Smith DE, Eghtesada S, Meydani SN (1997) Vitamin E supplementation decreases lung virus titers in mice infected with influenza. J Infect Dis 176:273–276PubMedCrossRefGoogle Scholar
  17. Hosono R, Sato Y, Aizawa SI, Mitsui Y (1980) Age-dependent changes in mobility and separation of the nematode Caenorhabditis elegans. Exp Gerontol 15:285–289PubMedCrossRefGoogle Scholar
  18. Hsin H, Kenyon C (1999) Signals from the reproductive system regulate the lifespan of C. elegans. Nature 399:362–366PubMedCrossRefGoogle Scholar
  19. Ikeda T, Yasui C, Hoshino K, Arikawa K, Nishikawa Y (2007) Influence of lactic acid bacteria on longevity of Caenorhabditis elegans and host defense against Salmonella entetica serovar Enteritidis. Appl Environ Microbiol 73:6404–6409PubMedCrossRefGoogle Scholar
  20. Ingram DK, Zhu M, Mamczarz J, Zou S, Lane MA, Roth GS, deCabo R (2006) Calorie restriction mimetics: an emerging research field. Aging Cell 5:97–108PubMedCrossRefGoogle Scholar
  21. Inoue H, Hisamoto N, An JH, Oliveira RP, Nishida E, Blackwell TK, Matsumoto K (2005) The C. elegans p38 MAPK pathway regulates nuclear localization of the transcription factor SKN-1 in oxidative stress response. Genes Dev 19:2278–2283PubMedCrossRefGoogle Scholar
  22. Kim Y, Mylonakis E (2012) Caenorhabditis elegans immune conditioning with the probiotic bacterium Lactobacillus acidophilus strain NCFM enhances Gram-positive immune responses. Infect Immun 80:2500–2508PubMedCrossRefGoogle Scholar
  23. Kim DH, Liberati NT, Mizuno T, Inoue H, Hisamoto N, Matsumoto K, Ausubel FM (2004) Integration of Caenorhabditis elegans MAPK pathways mediating immunity and stress resistance by MEK-1 MAPK kinase and VHP-1 MAPK phosphatase. Proc Natl Acad Sci U S A 101:10990–10994PubMedCrossRefGoogle Scholar
  24. Komura T, Yasui C, Miyamoto H, Nishikawa Y (2010) Caenorhabditis elegans as an alternative model host for Legionella pneumophila and the protective effects of Bifidobacterium infantis. Appl Environ Microbiol 76:4105–4108PubMedCrossRefGoogle Scholar
  25. Komura T, Ikeda T, Hoshino K, Shibamura A, Nishikawa Y (2012) Caenorhabditis elegans as an alternative model to study senescence of host defense and the prevention by immunonutrition. Adv Exp Med Biol 710:19–27PubMedCrossRefGoogle Scholar
  26. Lee SS, Kennedy S, Tolonen AC, Ruvkun G (2003) DAF-16 target genes that control C. elegans life-span and metabolism. Science 300:644–647PubMedCrossRefGoogle Scholar
  27. Lee J, Yun HS, Cho KW, Oh S, Kim SH, Chun T, Kim B, Whang KY (2011) Evaluation of probiotic characteristics of newly isolated Lactobacillus spp.: immune modulation and longevity. Int J Food Microbiol 148:80–86PubMedCrossRefGoogle Scholar
  28. Lee-Wickner LJ, Chassy BM (1984) Production and regeneration of Lactobacillus casei protoplasts. Appl Environ Microbiol 48:994–1000PubMedGoogle Scholar
  29. Marsh EK, van den Berg MC, May RC (2011) A two-gene balance regulates Salmonella typhimurium tolerance in the nematode Caenorhabditis elegans. PLoS ONE 6:e16839PubMedCrossRefGoogle Scholar
  30. McColl G, Rogers AN, Alavez S, Hubbard AE, Melov S, Link CD, Bush AI, Kapahi P, Lithgow GJ (2010) Insulin-like signaling determines survival during stress via posttranscriptional mechanisms in C. elegans. Cell Metab 12:260–272PubMedCrossRefGoogle Scholar
  31. Metchnikoff E (1907) The Prolongation of Life. Heinemann, LondonGoogle Scholar
  32. Miller E, Gay N (1997) Effect of age on outcome and epidemiology of infectious diseases. Biologicals 25:137–142PubMedCrossRefGoogle Scholar
  33. Moulias R, Devillechabrolle A, Lesourd B, Proust J, Marescot MR, Doumerc S, Favre Berrone M, Congy F, Wang A (1985) Respective roles of immune and nutritional factors in the priming of the immune response in the elderly. Mech Ageing Dev 31:123–137PubMedCrossRefGoogle Scholar
  34. 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
  35. Naidu AS, Bidlack WR, Clemens RA (1999) Probiotic spectra of lactic acid bacteria (LAB). Crit Rev Food Sci Nutr 39:13–126PubMedCrossRefGoogle Scholar
  36. 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 U S A 102:4494–4499PubMedCrossRefGoogle Scholar
  37. Okuyama T, Inoue H, Ookuma S, Satoh T, Kano K, Honjoh S, Hisamoto N, Matsumoto K, Nishida E (2010) The ERK-MAPK pathway regulates longevity through SKN-1 and insulin-like signaling in Caenorhabditis elegans. J Biol Chem 285:30274–30281PubMedCrossRefGoogle Scholar
  38. Oliveira RP, Porter Abate J, Dilks K, Landis J, Ashraf J, Murphy CT, Blackwell TK (2009) Condition-adapted stress and longevity gene regulation by Caenorhabditis elegans SKN-1/Nrf. Aging Cell 8:524–541PubMedCrossRefGoogle Scholar
  39. Ottaviani E, Ventura N, Mandrioli M, Candela M, Franchini A, Franceschi C (2011) Gut microbiota as a candidate for lifespan extension: an ecological/evolutionary perspective targeted on living organisms as metaorganisms. Biogerontology 12:599–609PubMedCrossRefGoogle Scholar
  40. Papp D, Csermely P, Soti C (2012) A Role for SKN-1/Nrf in pathogen resistance and immunosenescence in Caenorhabditis elegans. PLoS Pathog 8:e1002673PubMedCrossRefGoogle Scholar
  41. Pawelec G, Larbi A (2008) Immunity and ageing in man: annual review 2006/2007. Exp Gerontol 43:34–38PubMedGoogle Scholar
  42. Pincus Z, Slack FJ (2010) Developmental biomarkers of aging in Caenorhabditis elegans. Dev Dyn 239:1306–1314PubMedGoogle Scholar
  43. Pop-Vicas A, Gravenstein S (2011) Influenza in the elderly—a mini-review. Gerontology 57:397–404PubMedGoogle Scholar
  44. Reinke SN, Hu X, Sykes BD, Lemire BD (2010) Caenorhabditis elegans diet significantly affects metabolic profile, mitochondrial DNA levels, lifespan and brood size. Mol Genet Metab 100:274–282PubMedCrossRefGoogle Scholar
  45. Riddle DL, Blumenthal T, Meyer BJ, Priess JR (eds) (1997) C. elegans II. Cold Spring Harbor Laboratory Press, Cold Spring HarborGoogle Scholar
  46. Ristow M, Schmeisser S (2011) Extending life span by increasing oxidative stress. Free Radic Biol Med 51:327–336PubMedCrossRefGoogle Scholar
  47. Rutherfurd-Markwick KJ, Gill HS (2004) Probiotics and immunomodulation. In: Hughes DA, Darlington LG, Bendich A (eds) Diet and human immune function. Humana Press, Totowa, pp 327–344CrossRefGoogle Scholar
  48. Shinzawa N, Nelson B, Aonuma H, Okado K, Fukumoto S, Miura M, Kanuka H (2009) p38 MAPK-dependentphagocytic encapsulation confers infection tolerance in Drosophila. Cell Host Microbe 6:244–252PubMedCrossRefGoogle Scholar
  49. Singh V, Aballay A (2006) Heat-shock transcription factor (HSF)-1 pathway required for Caenorhabditis elegans immunity. Proc Natl Acad Sci U S A 103:13092–13097Google Scholar
  50. Sligl WI, Majumdar SR (2011) How important is age in defining the prognosis of patients with community-acquired pneumonia? Curr Opin Infect Dis 24:142–147PubMedCrossRefGoogle Scholar
  51. Stiernagle T (1999) Maintenance of C. elegans. In: Hope IA (ed) C elegans: a practical approach. Oxford University Press, New York, pp 51–67Google Scholar
  52. Sulston J, Hodgkin J (1988) Methods. In: Wood WB (ed) The nematode Caenorhabditis elegans. Cold Spring Harbor Laboratory Press, New York, pp 587–606Google Scholar
  53. Tejada-Simon MV, Pestka JJ (1999) Proinflammatory cytokine and nitric oxide induction in murine macrophages by cell wall cytoplasmic extracts of lactic acid bacteria. J Food Prot 62:1435–1444PubMedGoogle Scholar
  54. Troemel ER, Chu SW, Reinke V, Lee SS, Ausubel FM, Kim DH (2006) p38 MAPK regulates expression of immune response genes and contributes to longevity in C. elegans. PLoS Genet 2:1725–1739CrossRefGoogle Scholar
  55. Tullet JM, Hertweck M, An JH, Baker J, Hwang JY, Liu S, Oliveira RP, Baumeister R, Blackwell TK (2008) Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans. Cell 132:1025–1038PubMedCrossRefGoogle Scholar
  56. Van der Hoeven R, McCallum KC, Cruz MR, Garsin DA (2011) Ce-Duox1/BLI-3 generated reactive oxygen species trigger protective SKN-1 activity via p38 MAPK signaling during Infection in C. elegans. PLoS Pathog 7:e1002453PubMedCrossRefGoogle Scholar
  57. Wang C, Wang J, Gong J, Yu H, Pacan JC, Niu Z, Si W, Sabour PM (2011) Use of Caenorhabditis elegans for preselecting Lactobacillus isolates to control Salmonella Typhimurium. J Food Prot 74:86–93PubMedCrossRefGoogle Scholar
  58. Wu D, Rea SL, Yashin AI, Johnson TE (2006) Visualizing hidden heterogeneity in isogenic populations of C. elegans. Exp Gerontol 41:261–270PubMedCrossRefGoogle Scholar
  59. Yang W, Li J, Hekimi S (2007) A Measurable increase in oxidative damage due to reduction in superoxide detoxification fails to shorten the life span of long-lived mitochondrial mutants of Caenorhabditis elegans. Genetics 177:2063–2074PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Tomomi Komura
    • 1
  • Takanori Ikeda
    • 1
  • Chikako Yasui
    • 1
  • Shigeru Saeki
    • 1
  • Yoshikazu Nishikawa
    • 1
  1. 1.Department of Food and Human Health Sciences, Graduate School of Human Life ScienceOsaka City UniversitySumiyoshi-ku, OsakaJapan

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