Skip to main content

Advertisement

Log in

NF-κB Signaling in the Aging Process

  • Published:
Journal of Clinical Immunology Aims and scope Submit manuscript

Abstract

Introduction

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.

Discussion

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.

Conclusion

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Troen BR. The biology of aging. Mt Sinai J Med. 2003;70:3–22.

    PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  8. Vijg J, Calder RB. Transcript of aging. Trends Genet. 2004;20:221–4. doi:10.1016/j.tig.2004.04.007.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  24. Hayden MS, Ghosh S. Signaling to NF-κB. Genes Dev. 2004;18:2195–224. doi:10.1101/gad.1228704.

    Article  PubMed  CAS  Google Scholar 

  25. Scheidereit C. IκB kinase complexes: gateways to NF-κB activation and transcription. Oncogene. 2006;25:6685–705. doi:10.1038/sj.onc.1209934.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  31. Harman D. Free radical theory of aging. Mutat Res. 1992;275:257–66.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  38. Danilova N. The evolution of immune mechanisms. J Exp Zool. 2006;306B:496–520.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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. Trebilcock GU, Ponnappan U. Nuclear factor κB induction in CD45RO+ and CD45RA+ T cell subsets during aging. Mech Ageing Dev. 1998;102:149–63.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  49. Sinclair DA, Guarente L. Extrachromosomal rDNA circles—a cause of aging in yeast. Cell. 1997;91:1033–42.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  51. Michan S, Sinclair D. Sirtuins in mammals: insights into their biological function. Biochem J. 2007;404:1–13.

    Article  PubMed  CAS  Google Scholar 

  52. Guarente L. Sirtuins as potential targets for metabolic syndrome. Nature. 2006;444:868–74.

    Article  PubMed  CAS  Google Scholar 

  53. Longo VD, Kennedy BK. Sirtuins in aging and age-related disease. Cell. 2006;126:257–68.

    Article  PubMed  CAS  Google Scholar 

  54. Kwon HS, Ott M. The ups and downs of SIRT1. Trends Biochem Sci. 2008;33:517–25.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  58. Lombard DB, Schwer B, Alt FW, Mostoslavsky R. SIRT6 in DNA repair, metabolism and ageing. J Intern Med. 2008;263:128–41.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  61. Braeckman B, Vanfleteren JR. Genetic control of longevity in C. elegans. Exp Gerontol. 2007;42:90–8.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  63. Greer EL, Brunet A. FOXO transcription factors at the interface between longevity and tumor suppression. Oncogene. 2005;24:7410–25.

    Article  PubMed  CAS  Google Scholar 

  64. Coffer PJ, Burgering BMT. Forkhead-box transcription factors and their role in the immune system. Nat Rev Immunol. 2004;4:889–99.

    Article  PubMed  CAS  Google Scholar 

  65. Peng SL. Foxo in the immune system. Oncogene. 2008;27:2337–44.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  70. Belvin MP, Anderson KV. A conserved signaling pathway: the Drosophila Toll-Dorsal pathway. Annu Rev Cell Dev Biol. 1996;12:393–416.

    Article  PubMed  CAS  Google Scholar 

  71. Gauldie J. Inflammation and the aging process: devil or angel. Nutr Rev. 2007;65:S167–9.

    Article  PubMed  Google Scholar 

  72. Libby P. Inflammatory mechanisms: the molecular basis of inflammation and disease. Nutr Rev. 2007;65:S140–6.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  74. Delano MJ, Moldawer LL. The origins of cachexia in acute and chronic inflammatory diseases. Nutr Clin Pract. 2006;21:68–81.

    Article  PubMed  Google Scholar 

  75. Li H, Malhotra S, Kumar A. Nuclear factor-κB signaling in skeletal muscle atrophy. J Mol Med. 2008;86:1113–26.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  78. Wang E. Regulation of apoptosis resistance and ontogeny of age-dependent diseases. Exp Geront. 1997;32:471–84.

    Article  CAS  Google Scholar 

  79. Warner HR. Is cell death and replacement a factor in aging? Mech Age Dev. 2007;128:13–6.

    Article  CAS  Google Scholar 

  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. Cuervo AM. Autophagy and aging: keeping that old broom working. Trends Genet. 2008;24:604–12.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  84. Terman A, Brunk UT. Oxidative stress, accumulation of biological “garbage”, and aging. Antioxid Redox Signal. 2006;8:197–204.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  90. Bremner P, Heinrich M. Natural products as targeted modulators of the nuclear factor-kappaB pathway. J Pharm Pharmacol. 2002;54:453–72.

    Article  PubMed  CAS  Google Scholar 

  91. Rahman I, Biswas SK, Kirkham PA. Regulation of inflammation and redox signaling by dietary polyphenols. Biochem Pharmacol. 2006;72:1439–52.

    Article  PubMed  CAS  Google Scholar 

  92. Mattson MP, Cheng A. Neurohormetic phytochemicals: low-dose toxins that induce adaptive neuronal stress responses. Trends Neurosci. 2006;29:632–9.

    Article  PubMed  CAS  Google Scholar 

  93. Rattan SI. Hormesis in aging. Ageing Res Rev. 2008;7:63–78.

    Article  PubMed  Google Scholar 

  94. Shakibaei M, Harikumar KB, Aggarwal BB. Resveratrol addiction: to die or not to die. Mol Nutr Food Res. 2009;53:115–28.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  96. Bordone L, Guarente L. Calorie restriction, SIRT1 and metabolism: understanding longevity. Nat Rev Mol Cell Biol. 2005;6:298–305.

    Article  PubMed  CAS  Google Scholar 

  97. Morgan TE, Wong AM, Finch CE. Anti-inflammatory mechanisms of dietary restriction in slowing aging processes. Interdiscip Top Gerontol. 2007;35:83–97.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

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.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Antero Salminen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Salminen, A., Kaarniranta, K. NF-κB Signaling in the Aging Process. J Clin Immunol 29, 397–405 (2009). https://doi.org/10.1007/s10875-009-9296-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10875-009-9296-6

Keywords

Navigation