Journal of Clinical Immunology

, Volume 29, Issue 4, pp 397–405 | Cite as

NF-κB Signaling in the Aging Process

  • Antero Salminen
  • Kai Kaarniranta



The aging process represents a progressive decline in cellular and organism function. Explaining the aging process has given rise to a cornucopia for different theories in which the basic difference has been the question whether aging is genetically regulated or an entropic degeneration process.


Different screening techniques have revealed that mammalian aging is associated with the activation of NF-κB transcription factor system. The NF-κB system is an ancient host defense system concerned with immune responses and different external and internal dangers, such as oxidative and genotoxic stress. NF-κB signaling is not only the master regulator of inflammatory responses but can also regulate several homeostatic responses such as apoptosis, autophagy, and tissue atrophy. We will describe how chronic activation of NF-κB signaling has the capacity to induce the senescent phenotype associated with aging. Interestingly, several longevity genes such as SIRT1, SIRT6, and FoxOs can clearly suppress NF-κB signaling and in this way delay the aging process and extend lifespan.


It seems that the aging process is an entropic degeneration process driven by NF-κB signaling. This process can be regulated by a variety of longevity genes along with a plethora of other factors such as genetic polymorphism, immune and dietary aspects, and environmental insults.


Aging inflamm-aging longevity NF-κB SIRT1 Sirtuins 



This study was financially supported by grants from the Academy of Finland and the University of Kuopio, Finland. The authors thank Dr. Ewen MacDonald for checking the language of the manuscript.


  1. 1.
    Troen BR. The biology of aging. Mt Sinai J Med. 2003;70:3–22.PubMedGoogle Scholar
  2. 2.
    Finch CE, Ruvkun G. The genetics of aging. Annu Rev Genomics Hum Genet. 2001;2:435–62. doi: 10.1146/annurev.genom.2.1.435.PubMedCrossRefGoogle Scholar
  3. 3.
    Salminen A, Huuskonen J, Ojala J, Kauppinen A, Kaarniranta K, Suuronen T. Activation of innate immunity system during aging: NF-κB signaling is the culprit of inflamm-aging. Ageing Res Rev. 2008;7:83–105. doi: 10.1016/j.arr.2007.09.002.PubMedCrossRefGoogle Scholar
  4. 4.
    Hayflick L. Entropy explains aging, genetic determinism explains longevity, and undefined terminology explains misunderstanding both. PLoS Genet. 2007;3:e220. doi: 10.1371/journal.pgen.0030220.PubMedCrossRefGoogle Scholar
  5. 5.
    Capri M, Salvioli S, Sevini F, Valensin S, Celani L, Monti D, et al. The genetics of human longevity. Ann N Y Acad Sci. 2006;1067:252–63. doi: 10.1196/annals.1354.033.PubMedCrossRefGoogle Scholar
  6. 6.
    Warner HR. Longevity genes: from primitive organisms to humans. Mech Ageing Dev. 2005;126:235–42. doi: 10.1016/j.mad.2004.08.015.PubMedCrossRefGoogle Scholar
  7. 7.
    Smith ED, Kennedy BK, Kaeberlein M. Genome-wide identification of conserved longevity genes in yeast and worms. Mech Ageing Dev. 2007;128:106–11. doi: 10.1016/j.mad.2006.11.017.PubMedCrossRefGoogle Scholar
  8. 8.
    Vijg J, Calder RB. Transcript of aging. Trends Genet. 2004;20:221–4. doi: 10.1016/j.tig.2004.04.007.PubMedCrossRefGoogle Scholar
  9. 9.
    De Magalhaes JP, Curado J, Church GM. Meta-analysis of age-related gene expression profiles identifies common signatures of aging. Bioinformatics. 2009;25:875–81. doi: 10.1093/bioinformatics/btp073.PubMedCrossRefGoogle Scholar
  10. 10.
    Franceschi C, Valesin S, Bonafe M, Paolisso G, Yashin AI, Monti D, et al. The network and the remodeling theories of aging: historical background and new perspectives. Exp Gerontol. 2000;35:879–96. doi: 10.1016/S0531-5565(00)00172-8.PubMedCrossRefGoogle Scholar
  11. 11.
    Helenius M, Hanninen M, Lehtinen SK, Salminen A. Changes associated with aging and replicative senescence in the regulation of transcription factor nuclear factor-κB. Biochem J. 1996;318:603–8.PubMedGoogle Scholar
  12. 12.
    Helenius M, Hanninen M, Lehtinen SK, Salminen A. Aging-induced up-regulation of nuclear binding activities of oxidative stress responsive NF-κB transcription factor in mouse cardiac muscle. J Mol Cell Cardiol. 1996;28:487–98. doi: 10.1006/jmcc.1996.0045.PubMedCrossRefGoogle Scholar
  13. 13.
    Korhonen P, Helenius M, Salminen A. Age-related changes in the regulation of transcription factor NF-κB in rat brain. Neurosci Lett. 1997;225:61–4. doi: 10.1016/S0304-3940(97)00190-0.PubMedCrossRefGoogle Scholar
  14. 14.
    Helenius M, Kyrylenko S, Vehvilainen P, Salminen A. Characterization of aging-associated up-regulation of constitutive nuclear factor-κB binding activity. Antioxid Redox Signal. 2001;3:147–56. doi: 10.1089/152308601750100669.PubMedCrossRefGoogle Scholar
  15. 15.
    Roy AK, Vellanoweth RL, Chen S, Supakar PC, Jung MH, Song CS, et al. The evolutionary tangle of aging, sex, and reproduction and an experimental approach to its molecular dissection. Exp Gerontol. 1996;31:83–94. doi: 10.1016/0531-5565(95)00020-8.PubMedCrossRefGoogle Scholar
  16. 16.
    Spencer NFL, Poynter ME, Im SY, Daynes RA. Constitutive activation of NF-κB in an animal model of aging. Int Immunol. 1997;9:1581–8. doi: 10.1093/intimm/9.10.1581.PubMedCrossRefGoogle Scholar
  17. 17.
    Poynter ME, Daynes RA. Peroxisome proliferator-activated receptor alpha activation modulates cellular redox status, represses nuclear factor-κB signaling, and reduces inflammatory cytokine production in aging. J Biol Chem. 1998;273:32833–41. doi: 10.1074/jbc.273.49.32833.PubMedCrossRefGoogle Scholar
  18. 18.
    Kim HJ, Kim KW, Yu BP, Chung HY. The effect of age on cyclooxygenase-2 gene expression: NF-κB activation and IκBα degradation. Free Radic Biol Med. 2000;28:683–92. doi: 10.1016/S0891-5849(99)00274-9.PubMedCrossRefGoogle Scholar
  19. 19.
    Giardina C, Hubbard AK. Growing old with nuclear factor-κB. Cell Stress Chaperones. 2002;7:207–12. doi: 10.1379/1466-1268(2002)007<0207:GOWNFB>2.0.CO;2.PubMedCrossRefGoogle Scholar
  20. 20.
    Gosselin K, Abbadie C. Involvement of Rel/NF-κB transcription factors in senescence. Exp Gerontol. 2003;38:1271–83. doi: 10.1016/j.exger.2003.09.007.PubMedCrossRefGoogle Scholar
  21. 21.
    Adler AS, Sinha S, Kawahara TLA, Zhang JY, Segal E, Chang HY. Motif module map reveals enforcement of aging by continual NF-κB activity. Genes Dev. 2007;21:3244–57. doi: 10.1101/gad.1588507.PubMedCrossRefGoogle Scholar
  22. 22.
    Sen R, Baltimore D. Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell. 1986;46:705–16. doi: 10.1016/0092-8674(86)90346-6.PubMedCrossRefGoogle Scholar
  23. 23.
    Chen LF, Greene W. Shaping the nuclear action of NF-κB. Nat Rev Mol Cell Biol. 2004;5:392–401. doi: 10.1038/nrm1368.PubMedCrossRefGoogle Scholar
  24. 24.
    Hayden MS, Ghosh S. Signaling to NF-κB. Genes Dev. 2004;18:2195–224. doi: 10.1101/gad.1228704.PubMedCrossRefGoogle Scholar
  25. 25.
    Scheidereit C. IκB kinase complexes: gateways to NF-κB activation and transcription. Oncogene. 2006;25:6685–705. doi: 10.1038/sj.onc.1209934.PubMedCrossRefGoogle Scholar
  26. 26.
    Perkins ND. Integrating cell-signalling pathways with NF-κB and IKK function. Nat Rev Mol Cell Biol. 2007;8:49–62. doi: 10.1038/nrm2083.PubMedCrossRefGoogle Scholar
  27. 27.
    Sebban H, Yamaoka S, Courtois G. Posttranslational modifications of NEMO and its partners in NF-kappaB signaling. Trends Cell Biol. 2006;16:569–77. doi: 10.1016/j.tcb.2006.09.004.PubMedCrossRefGoogle Scholar
  28. 28.
    Janssens S, Tschopp J. Signals from within: the DNA-damage-induced NF-κB response. Cell Death Differ. 2006;13:773–84. doi: 10.1038/sj.cdd.4401843.PubMedCrossRefGoogle Scholar
  29. 29.
    Salminen A, Suuronen T, Huuskonen J, Kaarniranta K. NEMO shuttle: a link between DNA damage and NF-κB activation in progeroid syndromes? Biochem Biophys Res Commun. 2008;367:715–8. doi: 10.1016/j.bbrc.2007.11.189.PubMedCrossRefGoogle Scholar
  30. 30.
    Schreck R, Albermann K, Baeuerle PA. Nuclear factor κB: an oxidative stress-responsive transcription factor of eukaryotic cells (a review). Free Radic Res Commun. 1992;17:221–37. doi: 10.3109/10715769209079515.PubMedCrossRefGoogle Scholar
  31. 31.
    Harman D. Free radical theory of aging. Mutat Res. 1992;275:257–66.PubMedGoogle Scholar
  32. 32.
    Martin GM, Austad SN, Johnson TE. Genetic analysis of ageing: role of oxidative damage and environmental stresses. Nat Genet. 1996;13:25–34. doi: 10.1038/ng0596-25.PubMedCrossRefGoogle Scholar
  33. 33.
    Gloire G, Legrand-Poels S, Piette JNF. κB activation by reactive oxygen species: fifteen years later. Biochem Pharmacol. 2006;72:1493–505. doi: 10.1016/j.bcp.2006.04.011.PubMedCrossRefGoogle Scholar
  34. 34.
    Wuerzberger-Davis SM, Nakamura Y, Seufzer BJ, Miyamoto SNF. κB activation by combinations of NEMO SUMOylation and ATM activation stresses in the absence of DNA damage. Oncogene. 2007;26:641–51. doi: 10.1038/sj.onc.1209815.PubMedCrossRefGoogle Scholar
  35. 35.
    Rabe JH, Mamelak AJ, McElgunn PJS, Morison WL, Sauder DN. Photoaging: mechanisms and repair. J Am Acad Dermatol. 2006;55:1–19. doi: 10.1016/j.jaad.2005.05.010.PubMedCrossRefGoogle Scholar
  36. 36.
    Tanaka K, Hasegawa J, Asamitsu K, Okamoto T. Prevention of the ultraviolet B-mediated skin photoaging by a nuclear factor κB inhibitor, parthenolide. J Pharmacol Exp Ther. 2005;315:624–30. doi: 10.1124/jpet.105.088674.PubMedCrossRefGoogle Scholar
  37. 37.
    Trinchieri G, Sher A. Cooperation of Toll-like receptor signals in innate immune defence. Nat Rev Immunol. 2007;7:179–90. doi: 10.1038/nri2038.PubMedCrossRefGoogle Scholar
  38. 38.
    Danilova N. The evolution of immune mechanisms. J Exp Zool. 2006;306B:496–520.CrossRefGoogle Scholar
  39. 39.
    Friedman R, Hughes AL. Molecular evolution of the NF-kappaB signaling system. Immunogenet. 2002;53:964–74. doi: 10.1007/s00251-001-0399-3.CrossRefGoogle Scholar
  40. 40.
    Bianchi ME. DAMPs, PAMPs and alarmins: all we need to know about danger. J Leukoc Biol. 2007;81:1–5. doi: 10.1189/jlb.0306164.PubMedCrossRefGoogle Scholar
  41. 41.
    Medzhitov R, Janeway C Jr. Innate immune recognition: mechanisms and pathways. Immunol Rev. 2000;173:89–97. doi: 10.1034/j.1600-065X.2000.917309.x.PubMedCrossRefGoogle Scholar
  42. 42.
    Salminen A, Ojala J, Kauppinen A, Kaarniranta K, Suuronen T. Inflammation in Alzheimer's disease. Amyloid-ß oligomers trigger innate immunity defence via pattern recognition receptors. Prog Neurobiol. 2009;87:181–94. doi: 10.1016/j.pneurobio.2009.01.001.PubMedCrossRefGoogle Scholar
  43. 43.
    Larbi A, Franceschi C, Mazzatti D, Solana R, Wikby A, Pawelek G. Aging of the immune system as a prognostic factor for human longevity. Physiology (Bethesda). 2008;23:64–74. doi: 10.1152/physiol.00040.2007.Google Scholar
  44. 44.
    Caamano J, Hunter CANF. κB family of transcription factors: central regulators of innate and adaptive immune functions. Clin Microbiol Rev. 2002;15:414–29. doi: 10.1128/CMR.15.3.414-429.2002.PubMedCrossRefGoogle Scholar
  45. 45.
    Liang Y, Zhou Y, Shen P. NF-κB and its regulation on the immune system. Cell Mol Immunol. 2004;5:343–50.Google Scholar
  46. 46.
    Trebilcock GU, Ponnappan U. Nuclear factor κB induction in CD45RO+ and CD45RA+ T cell subsets during aging. Mech Ageing Dev. 1998;102:149–63.PubMedCrossRefGoogle Scholar
  47. 47.
    Helenius M, Makelainen L, Salminen A. Attenuation of NF-κB signaling response to UVB light during cellular senescence. Exp Cell Res. 1999;248:194–202.PubMedCrossRefGoogle Scholar
  48. 48.
    Huang MC, Liao JJ, Bonasera S, Longo DL, Goetzl EJ. Nuclear factor-κB-dependent reversal of aging-induced alterations in T cell cytokines. FASEB J. 2008;22:2142–50.PubMedCrossRefGoogle Scholar
  49. 49.
    Sinclair DA, Guarente L. Extrachromosomal rDNA circles—a cause of aging in yeast. Cell. 1997;91:1033–42.PubMedCrossRefGoogle Scholar
  50. 50.
    Kaeberlein M, McVey M, Guarente L. The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev. 1999;13:2570–80.PubMedCrossRefGoogle Scholar
  51. 51.
    Michan S, Sinclair D. Sirtuins in mammals: insights into their biological function. Biochem J. 2007;404:1–13.PubMedCrossRefGoogle Scholar
  52. 52.
    Guarente L. Sirtuins as potential targets for metabolic syndrome. Nature. 2006;444:868–74.PubMedCrossRefGoogle Scholar
  53. 53.
    Longo VD, Kennedy BK. Sirtuins in aging and age-related disease. Cell. 2006;126:257–68.PubMedCrossRefGoogle Scholar
  54. 54.
    Kwon HS, Ott M. The ups and downs of SIRT1. Trends Biochem Sci. 2008;33:517–25.PubMedCrossRefGoogle Scholar
  55. 55.
    Yeung F, Hoberg JE, Ramsey CS, Keller MD, Jones DR, Frye RA, et al. Modulation of NF-κB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J. 2004;23:2369–80.PubMedCrossRefGoogle Scholar
  56. 56.
    Yang SR, Wright J, Bauter M, Seweryniak K, Kode A, Rahman I. Sirtuin regulates cigarette smoke-induced proinflammatory mediator release via RelA/p65 NF-kappaB in macrophages in vitro and in rat lungs in vivo: implications for chronic inflammation and aging. Am J Physiol Lung Cell Mol Physiol. 2007;292:L567–76.PubMedCrossRefGoogle Scholar
  57. 57.
    Kwon HS, Brent MM, Getachew R, Jayakumar P, Chen LF, Schnolzer M, et al. Human immunodeficiency virus type 1 Tat protein inhibits the SIRT1 deacetylase and induces T cell hyperactivation. Cell Host Microbe. 2008;3:158–67.PubMedCrossRefGoogle Scholar
  58. 58.
    Lombard DB, Schwer B, Alt FW, Mostoslavsky R. SIRT6 in DNA repair, metabolism and ageing. J Intern Med. 2008;263:128–41.PubMedGoogle Scholar
  59. 59.
    Mostoslavsky R, Chua KF, Lombard DB, Pang WW, Fischer MR, Gellon L, et al. Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Cell. 2006;124:315–29.PubMedCrossRefGoogle Scholar
  60. 60.
    Kawahara TLA, Michishita E, Adler AS, Damian M, Berber E, Lin M, et al. SIRT6 links histone H3 lysine 9 deacetylation to NF-κB-dependent gene expression and organismal life span. Cell. 2009;136:62–74.PubMedCrossRefGoogle Scholar
  61. 61.
    Braeckman B, Vanfleteren JR. Genetic control of longevity in C. elegans. Exp Gerontol. 2007;42:90–8.PubMedCrossRefGoogle Scholar
  62. 62.
    Burnell AM, Houthoofd K, O'Hanlon K, Vanfleteren JR. Alternate metabolism during the dauer stage of the nematode Caenorhabditis elegans. Exp Gerontol. 2005;40:850–6.PubMedCrossRefGoogle Scholar
  63. 63.
    Greer EL, Brunet A. FOXO transcription factors at the interface between longevity and tumor suppression. Oncogene. 2005;24:7410–25.PubMedCrossRefGoogle Scholar
  64. 64.
    Coffer PJ, Burgering BMT. Forkhead-box transcription factors and their role in the immune system. Nat Rev Immunol. 2004;4:889–99.PubMedCrossRefGoogle Scholar
  65. 65.
    Peng SL. Foxo in the immune system. Oncogene. 2008;27:2337–44.PubMedCrossRefGoogle Scholar
  66. 66.
    Lin L, Hron JD, Peng SL. Regulation of NF-kappaB, Th activation, and autoinflammation by the forkhead transcription factor Foxo3a. Immunity. 2004;21:203–13.PubMedCrossRefGoogle Scholar
  67. 67.
    Lee HY, Youn SW, Kim JY, Park KW, Hwang CI, Park WY, et al. FOXO3a turns the tumor necrosis factor receptor signaling towards apoptosis through reciprocal regulation of c-Jun N-terminal kinase and NF-κB. Arterioscler Thromb Vasc Biol. 2008;28:112–20.PubMedCrossRefGoogle Scholar
  68. 68.
    Berdichevsky A, Viswanathan M, Horvitz HR, Guarente L. C. elegans SIR-2.1 interacts with 14-3-3 proteins to activate DAF-16 and extend life span. Cell. 2006;125:1165–77.PubMedCrossRefGoogle Scholar
  69. 69.
    Salminen A, Ojala J, Huuskonen J, Kauppinen A, Suuronen T, Kaarniranta K. Interaction of aging-associated signaling cascades: inhibition of NF-κB signaling by longevity factors FoxOs and SIRT1. Cell Mol Life Sci. 2008;65:1049–58.PubMedCrossRefGoogle Scholar
  70. 70.
    Belvin MP, Anderson KV. A conserved signaling pathway: the Drosophila Toll-Dorsal pathway. Annu Rev Cell Dev Biol. 1996;12:393–416.PubMedCrossRefGoogle Scholar
  71. 71.
    Gauldie J. Inflammation and the aging process: devil or angel. Nutr Rev. 2007;65:S167–9.PubMedCrossRefGoogle Scholar
  72. 72.
    Libby P. Inflammatory mechanisms: the molecular basis of inflammation and disease. Nutr Rev. 2007;65:S140–6.PubMedCrossRefGoogle Scholar
  73. 73.
    Argiles JM, Busquets S, Felipe A, Lopez-Soriano FJ. Molecular mechanisms involved in muscle wasting in cancer and ageing: cachexia versus sarcopenia. Int J Biochem Cell Biol. 2005;37:1084–104.PubMedCrossRefGoogle Scholar
  74. 74.
    Delano MJ, Moldawer LL. The origins of cachexia in acute and chronic inflammatory diseases. Nutr Clin Pract. 2006;21:68–81.PubMedCrossRefGoogle Scholar
  75. 75.
    Li H, Malhotra S, Kumar A. Nuclear factor-κB signaling in skeletal muscle atrophy. J Mol Med. 2008;86:1113–26.PubMedCrossRefGoogle Scholar
  76. 76.
    Cai D, Frantz JD, Tawa NE Jr, Melendez PA, Oh BC, Lidov HGW, et al. IKKß/NF-κB activation causes severe muscle wasting in mice. Cell. 2004;119:285–98.PubMedCrossRefGoogle Scholar
  77. 77.
    Sandri M, Sandri C, Gilbert A, Skurk C, Calabria E, Picard A, et al. Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell. 2004;117:399–412.PubMedCrossRefGoogle Scholar
  78. 78.
    Wang E. Regulation of apoptosis resistance and ontogeny of age-dependent diseases. Exp Geront. 1997;32:471–84.CrossRefGoogle Scholar
  79. 79.
    Warner HR. Is cell death and replacement a factor in aging? Mech Age Dev. 2007;128:13–6.CrossRefGoogle Scholar
  80. 80.
    Salminen A, Kaarniranta K. Regulation of the aging process by autophagy. Trends Mol Med. 2009 doi: 10.1016/j.molmed.2009.03.004
  81. 81.
    Cuervo AM. Autophagy and aging: keeping that old broom working. Trends Genet. 2008;24:604–12.PubMedCrossRefGoogle Scholar
  82. 82.
    Dutta J, Fan Y, Gupta N, Fan G, Gelinas C. Current insights into the regulation of programmed cell death by NF-κB. Oncogene. 2006;25:6800–16.PubMedCrossRefGoogle Scholar
  83. 83.
    Papa S, Zazzeroni F, Pham CG, Bubici C, Franzoso G. Linking JNK signaling to NF-kappaB: a key to survival. J Cell Sci. 2004;117:5197–208.PubMedCrossRefGoogle Scholar
  84. 84.
    Terman A, Brunk UT. Oxidative stress, accumulation of biological “garbage”, and aging. Antioxid Redox Signal. 2006;8:197–204.PubMedCrossRefGoogle Scholar
  85. 85.
    Bergamini E, Cavallini G, Donati A, Gori Z. The role of autophagy in aging: its essential part in the anti-aging mechanism of caloric restriction. Ann NY Acad Sci. 2007;1114:69–78.PubMedCrossRefGoogle Scholar
  86. 86.
    Dan HC, Baldwin AS. Differential involvement of IκB kinases α and ß in cytokine- and insulin-induced mammalian target of rapamycin activation determined by Akt. J Immunol. 2008;180:7582–9.PubMedGoogle Scholar
  87. 87.
    Lee DF, Kuo HP, Chen CT, Hsu JM, Chou CK, Wei Y, et al. IKKß suppression of TSC1 links inflammation and tumor angiogenesis via the mTOR pathway. Cell. 2007;130:440–55.PubMedCrossRefGoogle Scholar
  88. 88.
    Lee IH, Cao L, Mostoslavsky R, Lombard DB, Liu J, Bruns NE, et al. A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. Proc Natl Acad Sci USA. 2008;105:3374–9.PubMedCrossRefGoogle Scholar
  89. 89.
    Salminen A, Lehtonen M, Suuronen T, Kaarniranta K, Huuskonen J. Terpenoids: natural inhibitors of NF-κB signaling with anti-inflammatory and anticancer potential. Cell Mol Life Sci. 2008;65:2979–99.PubMedCrossRefGoogle Scholar
  90. 90.
    Bremner P, Heinrich M. Natural products as targeted modulators of the nuclear factor-kappaB pathway. J Pharm Pharmacol. 2002;54:453–72.PubMedCrossRefGoogle Scholar
  91. 91.
    Rahman I, Biswas SK, Kirkham PA. Regulation of inflammation and redox signaling by dietary polyphenols. Biochem Pharmacol. 2006;72:1439–52.PubMedCrossRefGoogle Scholar
  92. 92.
    Mattson MP, Cheng A. Neurohormetic phytochemicals: low-dose toxins that induce adaptive neuronal stress responses. Trends Neurosci. 2006;29:632–9.PubMedCrossRefGoogle Scholar
  93. 93.
    Rattan SI. Hormesis in aging. Ageing Res Rev. 2008;7:63–78.PubMedCrossRefGoogle Scholar
  94. 94.
    Shakibaei M, Harikumar KB, Aggarwal BB. Resveratrol addiction: to die or not to die. Mol Nutr Food Res. 2009;53:115–28.PubMedCrossRefGoogle Scholar
  95. 95.
    Keifer JA, Guttridge DC, Ashburner BP, Baldwin AS Jr. Inhibition of NF-κB activity by thalidomide through suppression of IκB kinase activity. J Biol Chem. 2001;276:22382–7.PubMedCrossRefGoogle Scholar
  96. 96.
    Bordone L, Guarente L. Calorie restriction, SIRT1 and metabolism: understanding longevity. Nat Rev Mol Cell Biol. 2005;6:298–305.PubMedCrossRefGoogle Scholar
  97. 97.
    Morgan TE, Wong AM, Finch CE. Anti-inflammatory mechanisms of dietary restriction in slowing aging processes. Interdiscip Top Gerontol. 2007;35:83–97.PubMedGoogle Scholar
  98. 98.
    Weindruch R, Kayo T, Lee CK, Prolla TA. Microarray profiling of gene expression in aging and its alteration by caloric restriction in mice. J Nutr. 2001;131:918S–23S.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of Neurology, Institute of Clinical MedicineUniversity of KuopioKuopioFinland
  2. 2.Department of NeurologyKuopio University HospitalKuopioFinland
  3. 3.Department of Ophthalmology, Institute of Clinical MedicineUniversity of KuopioKuopioFinland
  4. 4.Department of OphthalmologyKuopio University HospitalKuopioFinland

Personalised recommendations