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Immune Senescence and Inflammaging in Neurological Diseases

  • Pascale Baden
  • Silvia De Cicco
  • Cong Yu
  • Michela Deleidi
Living reference work entry

Abstract

Aging predisposes to disease via several mechanisms that in part converge on inflammatory pathways. As we age, the immune system undergoes a process of senescence accompanied by a chronic inflammatory environment named as “inflammaging”. Emerging evidence suggests that immune senescence also affects the central nervous system and promotes neuronal dysfunction and disease. This chapter focuses on immune senescence and inflammaging and their potential role in the etiopathogenesis of neurological diseases. A better understanding of the mechanisms involved in age-related immune dysfunction may help design novel therapeutic strategies to promote healthy brain aging and treat neurological disorders.

Keywords

Brain-immune interactions Aging Immunosenescence Inflammation Neurological diseases 

References

  1. Aguilar-Valles A, Inoue W, Rummel C, Luheshi GN (2015) Obesity, adipokines and neuroinflammation. Neuropharmacology 96(Pt A):124–134.  https://doi.org/10.1016/j.neuropharm.2014.12.023 CrossRefPubMedGoogle Scholar
  2. Appay V, Fastenackels S, Katlama C, Ait-Mohand H, Schneider L, Guihot A, Keller M, Grubeck-Loebenstein B, Simon A, Lambotte O, Hunt PW, Deeks SG, Costagliola D, Autran B, Sauce D (2011) Old age and anti-cytomegalovirus immunity are associated with altered T-cell reconstitution in HIV-1-infected patients. AIDS 25(15):1813–1822.  https://doi.org/10.1097/QAD.0b013e32834640e6 CrossRefPubMedGoogle Scholar
  3. Arruda AP, Pers BM, Parlakgul G, Guney E, Inouye K, Hotamisligil GS (2014) Chronic enrichment of hepatic endoplasmic reticulum-mitochondria contact leads to mitochondrial dysfunction in obesity. Nat Med 20(12):1427–1435.  https://doi.org/10.1038/nm.3735 CrossRefPubMedPubMedCentralGoogle Scholar
  4. Beers DR, Henkel JS, Zhao W, Wang J, Huang A, Wen S, Liao B, Appel SH (2011) Endogenous regulatory T lymphocytes ameliorate amyotrophic lateral sclerosis in mice and correlate with disease progression in patients with amyotrophic lateral sclerosis. Brain 134(Pt 5):1293–1314CrossRefPubMedPubMedCentralGoogle Scholar
  5. Bhadra R, Cobb DA, Weiss LM, Khan IA (2013) Psychiatric disorders in toxoplasma seropositive patients – the CD8 connection. Schizophr Bull 39(3):485–489.  https://doi.org/10.1093/schbul/sbt006 CrossRefPubMedPubMedCentralGoogle Scholar
  6. Bonotis K, Krikki E, Holeva V, Aggouridaki C, Costa V, Baloyannis S (2008) Systemic immune aberrations in Alzheimer’s disease patients. J Neuroimmunol 193(1–2):183–187CrossRefPubMedGoogle Scholar
  7. Brochard V, Combadiere B, Prigent A, Laouar Y, Perrin A, Beray-Berthat V, Bonduelle O, Alvarez-Fischer D, Callebert J, Launay JM, Duyckaerts C, Flavell RA, Hirsch EC, Hunot S (2009) Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease. J Clin Invest 119(1):182–192PubMedGoogle Scholar
  8. Burberry A, Suzuki N, Wang JY, Moccia R, Mordes DA, Stewart MH, Suzuki-Uematsu S, Ghosh S, Singh A, Merkle FT, Koszka K, Li QZ, Zon L, Rossi DJ, Trowbridge JJ, Notarangelo LD, Eggan K (2016) Loss-of-function mutations in the C9ORF72 mouse ortholog cause fatal autoimmune disease. Sci Transl Med 8(347):347ra393.  https://doi.org/10.1126/scitranslmed.aaf6038 CrossRefGoogle Scholar
  9. Calopa M, Bas J, Callen A, Mestre M (2010) Apoptosis of peripheral blood lymphocytes in Parkinson patients. Neurobiol Dis 38(1):1–7CrossRefPubMedGoogle Scholar
  10. Capuron L, Poitou C, Machaux-Tholliez D, Frochot V, Bouillot JL, Basdevant A, Laye S, Clement K (2011) Relationship between adiposity, emotional status and eating behaviour in obese women: role of inflammation. Psychol Med 41(7):1517–1528.  https://doi.org/10.1017/S0033291710001984 CrossRefPubMedGoogle Scholar
  11. Carter CJ (2009) Schizophrenia susceptibility genes directly implicated in the life cycles of pathogens: cytomegalovirus, influenza, herpes simplex, rubella, and Toxoplasma gondii. Schizophr Bull 35(6):1163–1182.  https://doi.org/10.1093/schbul/sbn054 CrossRefPubMedGoogle Scholar
  12. Cohen S, Janicki-Deverts D, Doyle WJ, Miller GE, Frank E, Rabin BS, Turner RB (2012) Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk. Proc Natl Acad Sci U S A 109(16):5995–5999.  https://doi.org/10.1073/pnas.1118355109 CrossRefPubMedPubMedCentralGoogle Scholar
  13. Correia-Melo C, Marques FD, Anderson R, Hewitt G, Hewitt R, Cole J, Carroll BM, Miwa S, Birch J, Merz A, Rushton MD, Charles M, Jurk D, Tait SW, Czapiewski R, Greaves L, Nelson G, Bohlooly YM, Rodriguez-Cuenca S, Vidal-Puig A, Mann D, Saretzki G, Quarato G, Green DR, Adams PD, von Zglinicki T, Korolchuk VI, Passos JF (2016) Mitochondria are required for pro-ageing features of the senescent phenotype. EMBO J 35(7):724–742. https://doi.org/10.15252/embj.201592862
  14. Cutuli D, De Bartolo P, Caporali P, Laricchiuta D, Foti F, Ronci M, Rossi C, Neri C, Spalletta G, Caltagirone C, Farioli-Vecchioli S, Petrosini L (2014) n-3 polyunsaturated fatty acids supplementation enhances hippocampal functionality in aged mice. Front Aging Neurosci 6:220.  https://doi.org/10.3389/fnagi.2014.00220 CrossRefPubMedPubMedCentralGoogle Scholar
  15. Damani MR, Zhao L, Fontainhas AM, Amaral J, Fariss RN, Wong WT (2011) Age-related alterations in the dynamic behavior of microglia. Aging Cell 10(2):263–276.  https://doi.org/10.1111/j.1474-9726.2010.00660.x CrossRefPubMedGoogle Scholar
  16. Deeks SG, Phillips AN (2009) HIV infection, antiretroviral treatment, ageing, and non-AIDS related morbidity. BMJ 338:a3172.  https://doi.org/10.1136/bmj.a3172 CrossRefPubMedGoogle Scholar
  17. Deleidi M, Gasser T (2013) The role of inflammation in sporadic and familial Parkinson’s disease. Cell Mol Life Sci 70(22):4259–4273.  https://doi.org/10.1007/s00018-013-1352-y CrossRefPubMedGoogle Scholar
  18. Deleidi M, Jaggle M, Rubino G (2015) Immune aging, dysmetabolism, and inflammation in neurological diseases. Front Neurosci 9:172.  https://doi.org/10.3389/fnins.2015.00172 CrossRefPubMedPubMedCentralGoogle Scholar
  19. Derhovanessian E, Maier AB, Beck R, Jahn G, Hahnel K, Slagboom PE, de Craen AJ, Westendorp RG, Pawelec G (2010) Hallmark features of immunosenescence are absent in familial longevity. J Immunol 185(8):4618–4624.  https://doi.org/10.4049/jimmunol.1001629 CrossRefPubMedGoogle Scholar
  20. Dupuis L, Pradat PF, Ludolph AC, Loeffler JP (2011) Energy metabolism in amyotrophic lateral sclerosis. Lancet Neurol 10(1):75–82.  https://doi.org/10.1016/S1474-4422(10)70224-6 CrossRefPubMedGoogle Scholar
  21. Eaton WW, Byrne M, Ewald H, Mors O, Chen CY, Agerbo E, Mortensen PB (2006) Association of schizophrenia and autoimmune diseases: linkage of Danish national registers. Am J Psychiatry 163(3):521–528.  https://doi.org/10.1176/appi.ajp.163.3.521 CrossRefPubMedGoogle Scholar
  22. Epel ES, Blackburn EH, Lin J, Dhabhar FS, Adler NE, Morrow JD, Cawthon RM (2004) Accelerated telomere shortening in response to life stress. Proc Natl Acad Sci U S A 101(49):17312–17315.  https://doi.org/10.1073/pnas.0407162101 CrossRefPubMedPubMedCentralGoogle Scholar
  23. Fiala M, Lin J, Ringman J, Kermani-Arab V, Tsao G, Patel A, Lossinsky AS, Graves MC, Gustavson A, Sayre J, Sofroni E, Suarez T, Chiappelli F, Bernard G (2005) Ineffective phagocytosis of amyloid-beta by macrophages of Alzheimer’s disease patients. J Alzheimers Dis 7(3):221–232; discussion 255–262Google Scholar
  24. Fontana L, Partridge L (2015) Promoting health and longevity through diet: from model organisms to humans. Cell 161(1):106–118.  https://doi.org/10.1016/j.cell.2015.02.020 CrossRefPubMedPubMedCentralGoogle Scholar
  25. Franceschi C, Capri M, Monti D, Giunta S, Olivieri F, Sevini F, Panourgia MP, Invidia L, Celani L, Scurti M, Cevenini E, Castellani GC, Salvioli S (2007) Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev 128(1):92–105.  https://doi.org/10.1016/j.mad.2006.11.016 CrossRefPubMedGoogle Scholar
  26. Fulop T, Larbi A, Pawelec G (2013) Human T cell aging and the impact of persistent viral infections. Front Immunol 4:271.  https://doi.org/10.3389/fimmu.2013.00271 CrossRefPubMedPubMedCentralGoogle Scholar
  27. Ghosh S, Lertwattanarak R, Lefort N, Molina-Carrion M, Joya-Galeana J, Bowen BP, Garduno-Garcia Jde J, Abdul-Ghani M, Richardson A, DeFronzo RA, Mandarino L, Van Remmen H, Musi N (2011) Reduction in reactive oxygen species production by mitochondria from elderly subjects with normal and impaired glucose tolerance. Diabetes 60(8):2051–2060.  https://doi.org/10.2337/db11-0121 CrossRefPubMedPubMedCentralGoogle Scholar
  28. Glaser R, Kiecolt-Glaser JK (2005) Stress-induced immune dysfunction: implications for health. Nat Rev Immunol 5(3):243–251.  https://doi.org/10.1038/nri1571 CrossRefPubMedGoogle Scholar
  29. Grozdanov V, Bliederhaeuser C, Ruf WP, Roth V, Fundel-Clemens K, Zondler L, Brenner D, Martin-Villalba A, Hengerer B, Kassubek J, Ludolph AC, Weishaupt JH, Danzer KM (2014) Inflammatory dysregulation of blood monocytes in Parkinson’s disease patients. Acta Neuropathol 128(5):651–663CrossRefPubMedPubMedCentralGoogle Scholar
  30. Guerreiro R, Wojtas A, Bras J, Carrasquillo M, Rogaeva E, Majounie E, Cruchaga C, Sassi C, Kauwe JS, Younkin S, Hazrati L, Collinge J, Pocock J, Lashley T, Williams J, Lambert JC, Amouyel P, Goate A, Rademakers R, Morgan K, Powell J, St George-Hyslop P, Singleton A, Hardy J, Alzheimer Genetic Analysis Group (2013) TREM2 variants in Alzheimer’s disease. N Engl J Med 368(2):117–127.  https://doi.org/10.1056/NEJMoa1211851 CrossRefPubMedGoogle Scholar
  31. Hagberg H, Mallard C, Ferriero DM, Vannucci SJ, Levison SW, Vexler ZS, Gressens P (2015) The role of inflammation in perinatal brain injury. Nat Rev Neurol 11(4):192–208.  https://doi.org/10.1038/nrneurol.2015.13 CrossRefPubMedPubMedCentralGoogle Scholar
  32. Handschin C, Spiegelman BM (2008) The role of exercise and PGC1alpha in inflammation and chronic disease. Nature 454(7203):463–469.  https://doi.org/10.1038/nature07206 CrossRefPubMedPubMedCentralGoogle Scholar
  33. Hefendehl JK, Neher JJ, Suhs RB, Kohsaka S, Skodras A, Jucker M (2014) Homeostatic and injury-induced microglia behavior in the aging brain. Aging Cell 13(1):60–69.  https://doi.org/10.1111/acel.12149 CrossRefPubMedGoogle Scholar
  34. Hong S, Banks WA (2015) Role of the immune system in HIV-associated neuroinflammation and neurocognitive implications. Brain Behav Immun 45:1–12.  https://doi.org/10.1016/j.bbi.2014.10.008 CrossRefPubMedGoogle Scholar
  35. Hotamisligil GS (2006) Inflammation and metabolic disorders. Nature 444(7121):860–867.  https://doi.org/10.1038/nature05485 CrossRefPubMedGoogle Scholar
  36. Hotamisligil GS, Shargill NS, Spiegelman BM (1993) Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259(5091):87–91CrossRefPubMedGoogle Scholar
  37. International Schizophrenia Consortium, Purcell SM, Wray NR, Stone JL, Visscher PM, O’Donovan MC, Sullivan PF, Sklar P (2009) Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 460(7256):748–752.  https://doi.org/10.1038/nature08185 PubMedCentralGoogle Scholar
  38. Itzhaki RF, Wozniak MA (2006) Herpes simplex virus type 1, apolipoprotein E, and cholesterol: a dangerous liaison in Alzheimer’s disease and other disorders. Prog Lipid Res 45(1):73–90.  https://doi.org/10.1016/j.plipres.2005.11.003 CrossRefPubMedGoogle Scholar
  39. Joachim CL, Selkoe DJ (1992) The seminal role of beta-amyloid in the pathogenesis of Alzheimer disease. Alzheimer Dis Assoc Disord 6(1):7–34CrossRefPubMedGoogle Scholar
  40. Jonsson T, Stefansson H, Steinberg S, Jonsdottir I, Jonsson PV, Snaedal J, Bjornsson S, Huttenlocher J, Levey AI, Lah JJ, Rujescu D, Hampel H, Giegling I, Andreassen OA, Engedal K, Ulstein I, Djurovic S, Ibrahim-Verbaas C, Hofman A, Ikram MA, van Duijn CM, Thorsteinsdottir U, Kong A, Stefansson K (2013) Variant of TREM2 associated with the risk of Alzheimer’s disease. N Engl J Med 368(2):107–116.  https://doi.org/10.1056/NEJMoa1211103 CrossRefPubMedGoogle Scholar
  41. Karabatsiakis A, Kolassa IT, Kolassa S, Rudolph KL, Dietrich DE (2014) Telomere shortening in leukocyte subpopulations in depression. BMC Psychiatry 14:192.  https://doi.org/10.1186/1471-244X-14-192 CrossRefPubMedPubMedCentralGoogle Scholar
  42. Kepp O, Galluzzi L, Kroemer G (2011) Mitochondrial control of the NLRP3 inflammasome. Nat Immunol 12(3):199–200.  https://doi.org/10.1038/ni0311-199 CrossRefPubMedGoogle Scholar
  43. Kiliaan AJ, Arnoldussen IA, Gustafson DR (2014) Adipokines: a link between obesity and dementia? Lancet Neurol 13(9):913–923.  https://doi.org/10.1016/S1474-4422(14)70085-7 CrossRefPubMedPubMedCentralGoogle Scholar
  44. Kim HK, Andreazza AC, Elmi N, Chen W, Young LT (2016) Nod-like receptor pyrin containing 3 (NLRP3) in the post-mortem frontal cortex from patients with bipolar disorder: a potential mediator between mitochondria and immune-activation. J Psychiatr Res 72:43–50.  https://doi.org/10.1016/j.jpsychires.2015.10.015 CrossRefPubMedGoogle Scholar
  45. Konner AC, Klockener T, Bruning JC (2009) Control of energy homeostasis by insulin and leptin: targeting the arcuate nucleus and beyond. Physiol Behav 97(5):632–638.  https://doi.org/10.1016/j.physbeh.2009.03.027 CrossRefPubMedGoogle Scholar
  46. Krysko DV, Agostinis P, Krysko O, Garg AD, Bachert C, Lambrecht BN, Vandenabeele P (2011) Emerging role of damage-associated molecular patterns derived from mitochondria in inflammation. Trends Immunol 32(4):157–164.  https://doi.org/10.1016/j.it.2011.01.005 CrossRefPubMedGoogle Scholar
  47. Laberge RM, Sun Y, Orjalo AV, Patil CK, Freund A, Zhou L, Curran SC, Davalos AR, Wilson-Edell KA, Liu S, Limbad C, Demaria M, Li P, Hubbard GB, Ikeno Y, Javors M, Desprez PY, Benz CC, Kapahi P, Nelson PS, Campisi J (2015) MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation. Nat Cell Biol 17(8):1049–1061.  https://doi.org/10.1038/ncb3195 CrossRefPubMedPubMedCentralGoogle Scholar
  48. Liao B, Zhao W, Beers DR, Henkel JS, Appel SH (2012) Transformation from a neuroprotective to a neurotoxic microglial phenotype in a mouse model of ALS. Exp Neurol 237(1):147–152.  https://doi.org/10.1016/j.expneurol.2012.06.011 CrossRefPubMedPubMedCentralGoogle Scholar
  49. Linton PJ, Dorshkind K (2004) Age-related changes in lymphocyte development and function. Nat Immunol 5(2):133–139.  https://doi.org/10.1038/ni1033 CrossRefPubMedGoogle Scholar
  50. Lynch MA (2010) Age-related neuroinflammatory changes negatively impact on neuronal function. Front Aging Neurosci 1:6.  https://doi.org/10.3389/neuro.24.006.2009 CrossRefPubMedPubMedCentralGoogle Scholar
  51. Maswood N, Young J, Tilmont E, Zhang Z, Gash DM, Gerhardt GA, Grondin R, Roth GS, Mattison J, Lane MA, Carson RE, Cohen RM, Mouton PR, Quigley C, Mattson MP, Ingram DK (2004) Caloric restriction increases neurotrophic factor levels and attenuates neurochemical and behavioral deficits in a primate model of Parkinson’s disease. Proc Natl Acad Sci U S A 101(52):18171–18176.  https://doi.org/10.1073/pnas.0405831102 CrossRefPubMedPubMedCentralGoogle Scholar
  52. Matheoud D, Sugiura A, Bellemare-Pelletier A, Laplante A, Rondeau C, Chemali M, Fazel A, Bergeron JJ, Trudeau LE, Burelle Y, Gagnon E, McBride HM, Desjardins M (2016) Parkinson’s disease-related proteins PINK1 and Parkin repress mitochondrial antigen presentation. Cell 166(2):314–327.  https://doi.org/10.1016/j.cell.2016.05.039 CrossRefPubMedGoogle Scholar
  53. Mercken EM, Crosby SD, Lamming DW, JeBailey L, Krzysik-Walker S, Villareal DT, Capri M, Franceschi C, Zhang Y, Becker K, Sabatini DM, de Cabo R, Fontana L (2013) Calorie restriction in humans inhibits the PI3K/AKT pathway and induces a younger transcription profile. Aging Cell 12(4):645–651.  https://doi.org/10.1111/acel.12088 CrossRefPubMedPubMedCentralGoogle Scholar
  54. Meyer-Luehmann M, Spires-Jones TL, Prada C, Garcia-Alloza M, de Calignon A, Rozkalne A, Koenigsknecht-Talboo J, Holtzman DM, Bacskai BJ, Hyman BT (2008) Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer’s disease. Nature 451(7179):720–724.  https://doi.org/10.1038/nature06616 CrossRefPubMedPubMedCentralGoogle Scholar
  55. Montgomery RR, Shaw AC (2015) Paradoxical changes in innate immunity in aging: recent progress and new directions. J Leukoc Biol 98(6):937–943.  https://doi.org/10.1189/jlb.5MR0315-104R CrossRefPubMedPubMedCentralGoogle Scholar
  56. Nakahira K, Haspel JA, Rathinam VA, Lee SJ, Dolinay T, Lam HC, Englert JA, Rabinovitch M, Cernadas M, Kim HP, Fitzgerald KA, Ryter SW, Choi AM (2011) Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Nat Immunol 12(3):222–230.  https://doi.org/10.1038/ni.1980 CrossRefPubMedGoogle Scholar
  57. Newsholme P, de Bittencourt PI Jr (2014) The fat cell senescence hypothesis: a mechanism responsible for abrogating the resolution of inflammation in chronic disease. Curr Opin Clin Nutr Metab Care 17(4):295–305.  https://doi.org/10.1097/MCO.0000000000000077 CrossRefPubMedGoogle Scholar
  58. O’Rourke JG, Bogdanik L, Yanez A, Lall D, Wolf AJ, Muhammad AK, Ho R, Carmona S, Vit JP, Zarrow J, Kim KJ, Bell S, Harms MB, Miller TM, Dangler CA, Underhill DM, Goodridge HS, Lutz CM, Baloh RH (2016) C9orf72 is required for proper macrophage and microglial function in mice. Science 351(6279):1324–1329.  https://doi.org/10.1126/science.aaf1064 CrossRefPubMedPubMedCentralGoogle Scholar
  59. Ott A, Stolk RP, van Harskamp F, Pols HA, Hofman A, Breteler MM (1999) Diabetes mellitus and the risk of dementia: the Rotterdam Study. Neurology 53(9):1937–1942CrossRefPubMedGoogle Scholar
  60. Painter MM, Atagi Y, Liu CC, Rademakers R, Xu H, Fryer JD, Bu G (2015) TREM2 in CNS homeostasis and neurodegenerative disease. Mol Neurodegener 10:43.  https://doi.org/10.1186/s13024-015-0040-9 CrossRefPubMedPubMedCentralGoogle Scholar
  61. Palacios N, Gao X, McCullough ML, Jacobs EJ, Patel AV, Mayo T, Schwarzschild MA, Ascherio A (2011) Obesity, diabetes, and risk of Parkinson’s disease. Mov Disord 26(12):2253–2259.  https://doi.org/10.1002/mds.23855 CrossRefPubMedPubMedCentralGoogle Scholar
  62. Patti ME, Butte AJ, Crunkhorn S, Cusi K, Berria R, Kashyap S, Miyazaki Y, Kohane I, Costello M, Saccone R, Landaker EJ, Goldfine AB, Mun E, DeFronzo R, Finlayson J, Kahn CR, Mandarino LJ (2003) Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: potential role of PGC1 and NRF1. Proc Natl Acad Sci U S A 100(14):8466–8471.  https://doi.org/10.1073/pnas.1032913100 CrossRefPubMedPubMedCentralGoogle Scholar
  63. Pearce BD, Valadi NM, Po CL, Miller AH (2000) Viral infection of developing GABAergic neurons in a model of hippocampal disinhibition. Neuroreport 11(11):2433–2438CrossRefPubMedGoogle Scholar
  64. Pellicano M, Larbi A, Goldeck D, Colonna-Romano G, Buffa S, Bulati M, Rubino G, Iemolo F, Candore G, Caruso C, Derhovanessian E, Pawelec G (2012) Immune profiling of Alzheimer patients. J Neuroimmunol 242(1–2):52–59.  https://doi.org/10.1016/j.jneuroim.2011.11.005 CrossRefPubMedGoogle Scholar
  65. Phillips C, Baktir MA, Srivatsan M, Salehi A (2014) Neuroprotective effects of physical activity on the brain: a closer look at trophic factor signaling. Front Cell Neurosci 8:170.  https://doi.org/10.3389/fncel.2014.00170 CrossRefPubMedPubMedCentralGoogle Scholar
  66. Pohl J, Woodside B, Luheshi GN (2014) Leptin modulates the late fever response to LPS in diet-induced obese animals. Brain Behav Immun 42:41–47.  https://doi.org/10.1016/j.bbi.2014.07.017 CrossRefPubMedGoogle Scholar
  67. Raj T, Rothamel K, Mostafavi S, Ye C, Lee MN, Replogle JM, Feng T, Lee M, Asinovski N, Frohlich I, Imboywa S, Von Korff A, Okada Y, Patsopoulos NA, Davis S, McCabe C, Paik HI, Srivastava GP, Raychaudhuri S, Hafler DA, Koller D, Regev A, Hacohen N, Mathis D, Benoist C, Stranger BE, De Jager PL (2014) Polarization of the effects of autoimmune and neurodegenerative risk alleles in leukocytes. Science 344(6183):519–523.  https://doi.org/10.1126/science.1249547 CrossRefPubMedPubMedCentralGoogle Scholar
  68. Santiago JA, Potashkin JA (2013) Shared dysregulated pathways lead to Parkinson’s disease and diabetes. Trends Mol Med 19(3):176–186.  https://doi.org/10.1016/j.molmed.2013.01.002 CrossRefPubMedGoogle Scholar
  69. Saunders JA, Estes KA, Kosloski LM, Allen HE, Dempsey KM, Torres-Russotto DR, Meza JL, Santamaria PM, Bertoni JM, Murman DL, Ali HH, Standaert DG, Mosley RL, Gendelman HE (2012) CD4+ regulatory and effector/memory T cell subsets profile motor dysfunction in Parkinson’s disease. J Neuroimmune Pharmacol 7(4):927–938CrossRefPubMedPubMedCentralGoogle Scholar
  70. Schwarcz R, Bruno JP, Muchowski PJ, Wu HQ (2012) Kynurenines in the mammalian brain: when physiology meets pathology. Nat Rev Neurosci 13(7):465–477.  https://doi.org/10.1038/nrn3257 CrossRefPubMedPubMedCentralGoogle Scholar
  71. Shimada K, Crother TR, Karlin J, Dagvadorj J, Chiba N, Chen S, Ramanujan VK, Wolf AJ, Vergnes L, Ojcius DM, Rentsendorj A, Vargas M, Guerrero C, Wang Y, Fitzgerald KA, Underhill DM, Town T, Arditi M (2012) Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis. Immunity 36(3):401–414.  https://doi.org/10.1016/j.immuni.2012.01.009 CrossRefPubMedPubMedCentralGoogle Scholar
  72. Simard AR, Soulet D, Gowing G, Julien JP, Rivest S (2006) Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer’s disease. Neuron 49(4):489–502.  https://doi.org/10.1016/j.neuron.2006.01.022 CrossRefPubMedGoogle Scholar
  73. Simon NM, Smoller JW, McNamara KL, Maser RS, Zalta AK, Pollack MH, Nierenberg AA, Fava M, Wong KK (2006) Telomere shortening and mood disorders: preliminary support for a chronic stress model of accelerated aging. Biol Psychiatry 60(5):432–435.  https://doi.org/10.1016/j.biopsych.2006.02.004 CrossRefPubMedGoogle Scholar
  74. Simopoulos AP (2002) The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomed Pharmacother 56(8):365–379CrossRefPubMedGoogle Scholar
  75. Skilton MR, Moulin P, Terra JL, Bonnet F (2007) Associations between anxiety, depression, and the metabolic syndrome. Biol Psychiatry 62(11):1251–1257.  https://doi.org/10.1016/j.biopsych.2007.01.012 CrossRefPubMedGoogle Scholar
  76. Steinman L (2004) Elaborate interactions between the immune and nervous systems. Nat Immunol 5(6):575–581.  https://doi.org/10.1038/ni1078 CrossRefPubMedGoogle Scholar
  77. Streit WJ, Xue QS (2014) Human CNS immune senescence and neurodegeneration. Curr Opin Immunol 29:93–96.  https://doi.org/10.1016/j.coi.2014.05.005 CrossRefPubMedGoogle Scholar
  78. Streit WJ, Braak H, Xue QS, Bechmann I (2009) Dystrophic (senescent) rather than activated microglial cells are associated with tau pathology and likely precede neurodegeneration in Alzheimer’s disease. Acta Neuropathol 118(4):475–485.  https://doi.org/10.1007/s00401-009-0556-6 CrossRefPubMedPubMedCentralGoogle Scholar
  79. Szekely CA, Breitner JC, Fitzpatrick AL, Rea TD, Psaty BM, Kuller LH, Zandi PP (2008) NSAID use and dementia risk in the Cardiovascular Health Study: role of APOE and NSAID type. Neurology 70(1):17–24.  https://doi.org/10.1212/01.wnl.0000284596.95156.48 CrossRefPubMedGoogle Scholar
  80. Szweda PA, Camouse M, Lundberg KC, Oberley TD, Szweda LI (2003) Aging, lipofuscin formation, and free radical-mediated inhibition of cellular proteolytic systems. Ageing Res Rev 2(4):383–405CrossRefPubMedGoogle Scholar
  81. Tchkonia T, Zhu Y, van Deursen J, Campisi J, Kirkland JL (2013) Cellular senescence and the senescent secretory phenotype: therapeutic opportunities. J Clin Invest 123(3):966–972.  https://doi.org/10.1172/JCI64098 CrossRefPubMedPubMedCentralGoogle Scholar
  82. Thaler JP, Yi CX, Schur EA, Guyenet SJ, Hwang BH, Dietrich MO, Zhao X, Sarruf DA, Izgur V, Maravilla KR, Nguyen HT, Fischer JD, Matsen ME, Wisse BE, Morton GJ, Horvath TL, Baskin DG, Tschop MH, Schwartz MW (2012) Obesity is associated with hypothalamic injury in rodents and humans. J Clin Invest 122(1):153–162.  https://doi.org/10.1172/JCI59660 CrossRefPubMedGoogle Scholar
  83. Thewissen M, Linsen L, Somers V, Geusens P, Raus J, Stinissen P (2005) Premature immunosenescence in rheumatoid arthritis and multiple sclerosis patients. Ann N Y Acad Sci 1051:255–262.  https://doi.org/10.1196/annals.1361.066 CrossRefPubMedGoogle Scholar
  84. Thewissen M, Somers V, Venken K, Linsen L, van Paassen P, Geusens P, Damoiseaux J, Stinissen P (2007) Analyses of immunosenescent markers in patients with autoimmune disease. Clin Immunol 123(2):209–218.  https://doi.org/10.1016/j.clim.2007.01.005 CrossRefPubMedGoogle Scholar
  85. Torrey EF, Bartko JJ, Yolken RH (2012) Toxoplasma gondii and other risk factors for schizophrenia: an update. Schizophr Bull 38(3):642–647.  https://doi.org/10.1093/schbul/sbs043 CrossRefPubMedPubMedCentralGoogle Scholar
  86. Trayhurn P, Wood IS (2004) Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br J Nutr 92(3):347–355CrossRefPubMedGoogle Scholar
  87. van Dooren FE, Schram MT, Schalkwijk CG, Stehouwer CD, Henry RM, Dagnelie PC, Schaper NC, van der Kallen CJ, Koster A, Sep SJ, Denollet J, Verhey FR, Pouwer F (2016) Associations of low grade inflammation and endothelial dysfunction with depression – the Maastricht Study. Brain Behav Immun 56:390–396.  https://doi.org/10.1016/j.bbi.2016.03.004 CrossRefPubMedGoogle Scholar
  88. von Bernhardi R, Tichauer JE, Eugenin J (2010) Aging-dependent changes of microglial cells and their relevance for neurodegenerative disorders. J Neurochem 112(5):1099–1114.  https://doi.org/10.1111/j.1471-4159.2009.06537.x CrossRefGoogle Scholar
  89. Wang Y, Ulland TK, Ulrich JD, Song W, Tzaferis JA, Hole JT, Yuan P, Mahan TE, Shi Y, Gilfillan S, Cella M, Grutzendler J, DeMattos RB, Cirrito JR, Holtzman DM, Colonna M (2016) TREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques. J Exp Med 213(5):667–675.  https://doi.org/10.1084/jem.20151948 CrossRefPubMedPubMedCentralGoogle Scholar
  90. Watkins CC, Treisman GJ (2012) Neuropsychiatric complications of aging with HIV. J Neurovirol 18(4):277–290.  https://doi.org/10.1007/s13365-012-0108-z CrossRefPubMedPubMedCentralGoogle Scholar
  91. West AP, Khoury-Hanold W, Staron M, Tal MC, Pineda CM, Lang SM, Bestwick M, Duguay BA, Raimundo N, MacDuff DA, Kaech SM, Smiley JR, Means RE, Iwasaki A, Shadel GS (2015) Mitochondrial DNA stress primes the antiviral innate immune response. Nature 520(7548):553–557.  https://doi.org/10.1038/nature14156 CrossRefPubMedPubMedCentralGoogle Scholar
  92. Wiley CD, Velarde MC, Lecot P, Liu S, Sarnoski EA, Freund A, Shirakawa K, Lim HW, Davis SS, Ramanathan A, Gerencser AA, Verdin E, Campisi J (2016) Mitochondrial dysfunction induces senescence with a distinct secretory phenotype. Cell Metab 23(2):303–314.  https://doi.org/10.1016/j.cmet.2015.11.011 CrossRefPubMedGoogle Scholar
  93. Witte AV, Fobker M, Gellner R, Knecht S, Floel A (2009) Caloric restriction improves memory in elderly humans. Proc Natl Acad Sci U S A 106(4):1255–1260.  https://doi.org/10.1073/pnas.0808587106 CrossRefPubMedPubMedCentralGoogle Scholar
  94. Wyss-Coray T (2006) Inflammation in Alzheimer disease: driving force, bystander or beneficial response? Nat Med 12(9):1005–1015.  https://doi.org/10.1038/nm1484 PubMedGoogle Scholar
  95. Xiang X, Werner G, Bohrmann B, Liesz A, Mazaheri F, Capell A, Feederle R, Knuesel I, Kleinberger G, Haass C (2016) TREM2 deficiency reduces the efficacy of immunotherapeutic amyloid clearance. EMBO Mol Med. http://dx.doi.org/10.15252/emmm.201606370
  96. Xie Z, Morgan TE, Rozovsky I, Finch CE (2003) Aging and glial responses to lipopolysaccharide in vitro: greater induction of IL-1 and IL-6, but smaller induction of neurotoxicity. Exp Neurol 182(1):135–141CrossRefPubMedGoogle Scholar
  97. Xu Q, Park Y, Huang X, Hollenbeck A, Blair A, Schatzkin A, Chen H (2011) Diabetes and risk of Parkinson’s disease. Diabetes Care 34(4):910–915.  https://doi.org/10.2337/dc10-1922 CrossRefPubMedPubMedCentralGoogle Scholar
  98. Ye SM, Johnson RW (2001) An age-related decline in interleukin-10 may contribute to the increased expression of interleukin-6 in brain of aged mice. Neuroimmunomodulation 9(4):183–192.  https://doi.org/10.1159/000049025 CrossRefPubMedGoogle Scholar
  99. Yolken RH, Torrey EF (2008) Are some cases of psychosis caused by microbial agents? A review of the evidence. Mol Psychiatry 13(5):470–479.  https://doi.org/10.1038/mp.2008.5 CrossRefPubMedGoogle Scholar
  100. Youm YH, Nguyen KY, Grant RW, Goldberg EL, Bodogai M, Kim D, D’Agostino D, Planavsky N, Lupfer C, Kanneganti TD, Kang S, Horvath TL, Fahmy TM, Crawford PA, Biragyn A, Alnemri E, Dixit VD (2015) The ketone metabolite beta-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. Nat Med 21(3):263–269.  https://doi.org/10.1038/nm.3804 PubMedPubMedCentralGoogle Scholar
  101. Zandi PP, Anthony JC, Hayden KM, Mehta K, Mayer L, Breitner JC, Cache County Study Investigators (2002) Reduced incidence of AD with NSAID but not H2 receptor antagonists: the Cache County Study. Neurology 59(6):880–886CrossRefPubMedGoogle Scholar
  102. Zhou R, Yazdi AS, Menu P, Tschopp J (2011) A role for mitochondria in NLRP3 inflammasome activation. Nature 469(7329):221–225.  https://doi.org/10.1038/nature09663 CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Pascale Baden
    • 1
    • 2
  • Silvia De Cicco
    • 1
    • 2
  • Cong Yu
    • 1
    • 2
  • Michela Deleidi
    • 1
    • 2
    • 3
    • 4
  1. 1.German Center for Neurodegenerative Diseases (DZNE)TübingenGermany
  2. 2.Center of Neurology, Hertie Institute for Clinical Brain Research, University of TübingenTübingenGermany
  3. 3.“Mitochondria and Inflammation in Neurodegenerative Diseases”German Center for Neurodegenerative Diseases (DZNE) Tübingen within the Helmholtz AssociationTübingenGermany
  4. 4.Department of Neurodegenerative DiseasesUniversity of TübingenTübingenGermany

Section editors and affiliations

  • Tamas Fulop
    • 1
  1. 1.Research Center on Aging, Department of Medicine, Immunology Graduate Programme, Faculty of MedicineUniversity of SherbrookeSherbrookeCanada

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