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The receptor for advanced glycation end-products (RAGE) is an important pattern recognition receptor (PRR) for inflammaging

  • Thibault TeissierEmail author
  • Éric Boulanger
Review Article

Abstract

The receptor for advanced glycation end-products (RAGE) was initially characterized and named for its ability to bind to advanced glycation end-products (AGEs) that form upon the irreversible and non-enzymatic interaction between nucleophiles, such as lysine, and carbonyl compounds, such as reducing sugars. The concentrations of AGEs are known to increase in conditions such as diabetes, as well as during ageing. However, it is now widely accepted that RAGE binds with numerous ligands, many of which can be defined as pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs). The interaction between RAGE and its ligands mainly results in a pro-inflammatory response, and can lead to stress events often favouring mitochondrial dysfunction or cellular senescence. Thus, RAGE should be considered as a pattern recognition receptor (PRR), similar to those that regulate innate immunity. Innate immunity itself plays a central role in inflammaging, the chronic low-grade and sterile inflammation that increases with age and is a potentially important contributory factor in ageing. Consequently, and in addition to the age-related accumulation of PAMPs and DAMPs and increases in pro-inflammatory cytokines from senescent cells and damaged cells, PRRs are therefore important in inflammaging. We suggest here that, through its interconnection with immunity, senescence, mitochondrial dysfunction and inflammasome activation, RAGE is a key contributor to inflammaging and that the pro-longevity effects seen upon blocking RAGE, or upon its deletion, are thus the result of reduced inflammaging.

Keywords

Ageing Inflammaging Receptor for advanced glycation end-products (RAGE) Pattern recognition receptor 

Notes

Acknowledgements

We are grateful to Mike Howsam for his contribution of editorial assistance and English proofreading.

We thank LES LABORATOIRES SERVIER who have shared, under the creative commons license, some of the graphic elements that were adapted for the figures herein.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Abedini A, Cao P, Plesner A, Zhang J, He M, Derk J, Patil SA, Rosario R, Lonier J, Song F et al (2018) RAGE binds preamyloid IAPP intermediates and mediates pancreatic β cell proteotoxicity. J Clin Invest 128:682–698CrossRefPubMedPubMedCentralGoogle Scholar
  2. Akchurin OM, Kaskel F (2015) Update on inflammation in chronic kidney disease. Blood Purif 39:84–92CrossRefPubMedGoogle Scholar
  3. Akirav EM, Preston-Hurlburt P, Garyu J, Henegariu O, Clynes R, Schmidt AM, Herold KC (2012) RAGE expression in human T cells: a link between environmental factors and adaptive immune responses. PLoS ONE 7:e34698CrossRefPubMedPubMedCentralGoogle Scholar
  4. Aquilano K, Vigilanza P, Baldelli S, Pagliei B, Rotilio G, Ciriolo MR (2010) Peroxisome proliferator-activated receptor γ Co-activator 1α (PGC-1α) and Sirtuin 1 (SIRT1) reside in mitochondria possible direct function in mitochondrial biogenesis. J Biol Chem 285:21590–21599CrossRefPubMedPubMedCentralGoogle Scholar
  5. Arai Y, Martin-Ruiz CM, Takayama M, Abe Y, Takebayashi T, Koyasu S, Suematsu M, Hirose N, von Zglinicki T (2015) Inflammation, but not telomere length, predicts successful ageing at extreme old age: a longitudinal study of semi-supercentenarians. EBioMedicine 2:1549–1558CrossRefPubMedPubMedCentralGoogle Scholar
  6. Austin S, St-Pierre J (2012) PGC1α and mitochondrial metabolism—emerging concepts and relevance in ageing and neurodegenerative disorders. J Cell Sci 125:4963–4971CrossRefPubMedGoogle Scholar
  7. Barile GR, Schmidt AM (2007) RAGE and its ligands in retinal disease. Curr Mol Med 7:758–765CrossRefPubMedGoogle Scholar
  8. Barlovic DP, Thomas MC, Jandeleit-Dahm K (2010) Cardiovascular disease: what’s all the AGE/RAGE about? Cardiovasc Hematol Disord 10:7–15CrossRefGoogle Scholar
  9. Bartling B, Hofmann H-S, Weigle B, Silber R-E, Simm A (2005) Down-regulation of the receptor for advanced glycation end-products (RAGE) supports non-small cell lung carcinoma. Carcinogenesis 26:293–301CrossRefPubMedGoogle Scholar
  10. Batkulwar K, Godbole R, Banarjee R, Kassaar O, Williams RJ, Kulkarni MJ (2018) Advanced glycation end products modulate amyloidogenic APP processing and tau phosphorylation: a mechanistic link between glycation and the development of Alzheimer’s disease. ACS Chem Neurosci 9:988–1000CrossRefPubMedGoogle Scholar
  11. Biagi E, Nylund L, Candela M, Ostan R, Bucci L, Pini E, Nikkïla J, Monti D, Satokari R, Franceschi C et al (2010) Through ageing, and beyond: gut microbiota and inflammatory status in seniors and centenarians. PLoS ONE 5:e10667CrossRefPubMedPubMedCentralGoogle Scholar
  12. Biagi E, Franceschi C, Rampelli S, Severgnini M, Ostan R, Turroni S, Consolandi C, Quercia S, Scurti M, Monti D et al (2016) Gut microbiota and extreme longevity. Curr Biol CB 26:1480–1485CrossRefPubMedGoogle Scholar
  13. Bianchi ME, Agresti A (2005) HMG proteins: dynamic players in gene regulation and differentiation. Curr Opin Genet Dev 15:496–506CrossRefPubMedGoogle Scholar
  14. Bianchi R, Giambanco I, Donato R (2010) S100B/RAGE-dependent activation of microglia via NF-kappaB and AP-1 Co-regulation of COX-2 expression by S100B, IL-1beta and TNF-alpha. Neurobiol Aging 31:665–677CrossRefPubMedGoogle Scholar
  15. Bierhaus A, Stern DM, Nawroth PP (2006) RAGE in inflammation: a new therapeutic target? Curr Opin Investig Drugs Lond Engl 2000(7):985–991Google Scholar
  16. Body-Malapel M, Djouina M, Waxin C, Langlois A, Gower-Rousseau C, Zerbib P, Schmidt A-M, Desreumaux P, Boulanger E, Vignal C (2019) The RAGE signaling pathway is involved in intestinal inflammation and represents a promising therapeutic target for Inflammatory Bowel Diseases. Mucosal Immunol 12:468–478CrossRefPubMedGoogle Scholar
  17. Bongarzone S, Savickas V, Luzi F, Gee AD (2017) Targeting the receptor for advanced glycation endproducts (RAGE): a medicinal chemistry perspective. J Med Chem 60:7213–7232CrossRefPubMedPubMedCentralGoogle Scholar
  18. Boulanger E, Wautier M-P, Wautier J-L, Boval B, Panis Y, Wernert N, Danze P-M, Dequiedt P (2002) AGEs bind to mesothelial cells via RAGE and stimulate VCAM-1 expression. Kidney Int 61:148–156CrossRefPubMedGoogle Scholar
  19. Boulanger E, Grossin N, Wautier M-P, Taamma R, Wautier J-L (2007) Mesothelial RAGE activation by AGEs enhances VEGF release and potentiates capillary tube formation. Kidney Int 71:126–133CrossRefPubMedGoogle Scholar
  20. Bresnick AR, Weber DJ, Zimmer DB (2015) S100 proteins in cancer. Nat Rev Cancer 15:96–109CrossRefPubMedPubMedCentralGoogle Scholar
  21. Brett J, Schmidt AM, Yan SD, Zou YS, Weidman E, Pinsky D, Nowygrod R, Neeper M, Przysiecki C, Shaw A et al (1993) Survey of the distribution of a newly characterized receptor for advanced glycation end products in tissues. Am J Pathol 143:1699–1712PubMedPubMedCentralGoogle Scholar
  22. Buckley ST, Ehrhardt C (2010) The receptor for advanced glycation end products (RAGE) and the lung. J Biomed Corp 3:3.  https://doi.org/10.1155/2010/917108 CrossRefGoogle Scholar
  23. Burstein AH, Sabbagh M, Andrews R, Valcarce C, Dunn I, Altstiel L (2018) Development of Azeliragon, an oral small molecule antagonist of the receptor for advanced glycation endproducts, for the potential slowing of loss of cognition in mild Alzheimer’s disease. J Prev Alzheimers Dis 5:149–154PubMedGoogle Scholar
  24. Burton DGA, Stolzing A (2018) Cellular senescence: immunosurveillance and future immunotherapy. Ageing Res Rev 43:17–25CrossRefPubMedGoogle Scholar
  25. Cai W, He JC, Zhu L, Chen X, Wallenstein S, Striker GE, Vlassara H (2007) Reduced oxidant stress and extended lifespan in mice exposed to a low glycotoxin diet: association with increased AGER1 expression. Am J Pathol 170:1893–1902CrossRefPubMedPubMedCentralGoogle Scholar
  26. Cai Z, Liu N, Wang C, Qin B, Zhou Y, Xiao M, Chang L, Yan L-J, Zhao B (2016) Role of RAGE in Alzheimer’s disease. Cell Mol Neurobiol 36:483–495CrossRefPubMedGoogle Scholar
  27. Candela P, Gosselet F, Saint-Pol J, Sevin E, Boucau M-C, Boulanger E, Cecchelli R, Fenart L (2010) Apical-to-basolateral transport of amyloid-β peptides through blood-brain barrier cells is mediated by the receptor for advanced glycation end-products and is restricted by P-glycoprotein. J Alzheimers Dis 22:849–859CrossRefPubMedGoogle Scholar
  28. Chavakis T, Bierhaus A, Al-Fakhri N, Schneider D, Witte S, Linn T, Nagashima M, Morser J, Arnold B, Preissner KT et al (2003) The pattern recognition receptor (RAGE) is a counterreceptor for leukocyte integrins. J Exp Med 198:1507–1515CrossRefPubMedPubMedCentralGoogle Scholar
  29. Chen Y, Akirav EM, Chen W, Henegariu O, Moser B, Desai D, Shen JM, Webster JC, Andrews RC, Mjalli AM et al (2008) RAGE ligation affects T cell activation and controls T cell differentiation. J Immunol Baltim Md 1950(181):4272–4278Google Scholar
  30. Chen J, Sun Z, Jin M, Tu Y, Wang S, Yang X, Chen Q, Zhang X, Han Y, Pi R (2017) Inhibition of AGEs/RAGE/Rho/ROCK pathway suppresses non-specific neuroinflammation by regulating BV2 microglial M1/M2 polarization through the NF-κB pathway. J Neuroimmunol 305:108–114CrossRefPubMedGoogle Scholar
  31. Cheng C, Tsuneyama K, Kominami R, Shinohara H, Sakurai S, Yonekura H, Watanabe T, Takano Y, Yamamoto H, Yamamoto Y (2005) Expression profiling of endogenous secretory receptor for advanced glycation end products in human organs. Mod Pathol 18:1385–1396CrossRefPubMedGoogle Scholar
  32. Comenzo RL (2000) Primary systemic amyloidosis. Curr Treat Opt Oncol 1:83–89CrossRefGoogle Scholar
  33. Coppé J-P, Desprez P-Y, Krtolica A, Campisi J (2010) The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol 5:99–118CrossRefPubMedPubMedCentralGoogle Scholar
  34. Correia-Melo C, Marques FDM, Anderson R, Hewitt G, Hewitt R, Cole J, Carroll BM, Miwa S, Birch J, Merz A et al (2016) Mitochondria are required for pro-ageing features of the senescent phenotype. EMBO J 35:724–742CrossRefPubMedPubMedCentralGoogle Scholar
  35. Coughlan MT, Thorburn DR, Penfold SA, Laskowski A, Harcourt BE, Sourris KC, Tan ALY, Fukami K, Thallas-Bonke V, Nawroth PP et al (2009) RAGE-induced cytosolic ROS promote mitochondrial superoxide generation in diabetes. J Am Soc Nephrol JASN 20:742–752CrossRefPubMedGoogle Scholar
  36. Crow YJ, Manel N (2015) Aicardi-Goutières syndrome and the type I interferonopathies. Nat Rev Immunol 15:429–440CrossRefPubMedGoogle Scholar
  37. Daroux M, Prévost G, Maillard-Lefebvre H, Gaxatte C, D’Agati VD, Schmidt AM, Boulanger E (2010) Advanced glycation end-products: implications for diabetic and non-diabetic nephropathies. Diabetes Metab 36:1–10CrossRefPubMedGoogle Scholar
  38. Davalos AR, Kawahara M, Malhotra GK, Schaum N, Huang J, Ved U, Beausejour CM, Coppe J-P, Rodier F, Campisi J (2013) p53-dependent release of Alarmin HMGB1 is a central mediator of senescent phenotypes. J Cell Biol 201:613–629CrossRefPubMedPubMedCentralGoogle Scholar
  39. de Gonzalo-Calvo D, Neitzert K, Fernández M, Vega-Naredo I, Caballero B, García-Macía M, Suárez FM, Rodríguez-Colunga MJ, Solano JJ, Coto-Montes A (2010) Differential inflammatory responses in aging and disease: TNF-alpha and IL-6 as possible biomarkers. Free Radic Biol Med 49:733–737CrossRefPubMedGoogle Scholar
  40. Deane R, Singh I, Sagare AP, Bell RD, Ross NT, LaRue B, Love R, Perry S, Paquette N, Deane RJ et al (2012) A multimodal RAGE-specific inhibitor reduces amyloid β-mediated brain disorder in a mouse model of Alzheimer disease. J Clin Invest 122:1377–1392CrossRefPubMedPubMedCentralGoogle Scholar
  41. Del Rio D, Stewart AJ, Pellegrini N (2005) A review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress. Nutr Metab Cardiovasc Dis NMCD 15:316–328CrossRefPubMedGoogle Scholar
  42. Demling N, Ehrhardt C, Kasper M, Laue M, Knels L, Rieber EP (2006) Promotion of cell adherence and spreading: a novel function of RAGE, the highly selective differentiation marker of human alveolar epithelial type I cells. Cell Tissue Res 323:475–488CrossRefPubMedGoogle Scholar
  43. Dinarello CA (2006) Interleukin 1 and interleukin 18 as mediators of inflammation and the aging process. Am J Clin Nutr 83:447S–455SCrossRefPubMedGoogle Scholar
  44. Ding Q, Keller JN (2005a) Splice variants of the receptor for advanced glycosylation end products (RAGE) in human brain. Neurosci Lett 373:67–72CrossRefPubMedGoogle Scholar
  45. Ding Q, Keller JN (2005b) Evaluation of rage isoforms, ligands, and signaling in the brain. Biochim Biophys. Acta BBA 1746:18–27CrossRefPubMedGoogle Scholar
  46. Dou Z, Ghosh K, Vizioli MG, Zhu J, Sen P, Wangensteen KJ, Simithy J, Lan Y, Lin Y, Zhou Z et al (2017) Cytoplasmic chromatin triggers inflammation in senescence and cancer. Nature 550:402–406CrossRefPubMedPubMedCentralGoogle Scholar
  47. Emanuele E, D’Angelo A, Tomaino C, Binetti G, Ghidoni R, Politi P, Bernardi L, Maletta R, Bruni AC, Geroldi D (2005) Circulating levels of soluble receptor for advanced glycation end products in Alzheimer disease and vascular dementia. Arch Neurol 62:1734–1736CrossRefPubMedGoogle Scholar
  48. Evankovich J, Cho SW, Zhang R, Cardinal J, Dhupar R, Zhang L, Klune JR, Zlotnicki J, Billiar T, Tsung A (2010) High mobility group box 1 release from hepatocytes during ischemia and reperfusion injury is mediated by decreased histone deacetylase activity. J Biol Chem 285:39888–39897CrossRefPubMedPubMedCentralGoogle Scholar
  49. Fagiolo U, Cossarizza A, Scala E, Fanales-Belasio E, Ortolani C, Cozzi E, Monti D, Franceschi C, Paganelli R (1993) Increased cytokine production in mononuclear cells of healthy elderly people. Eur J Immunol 23:2375–2378CrossRefPubMedGoogle Scholar
  50. Fang F, Lue L-F, Yan S, Xu H, Luddy JS, Chen D, Walker DG, Stern DM, Yan S, Schmidt AM et al (2010) RAGE-dependent signaling in microglia contributes to neuroinflammation, Abeta accumulation, and impaired learning/memory in a mouse model of Alzheimer’s disease. FASEB J 24:1043–1055CrossRefPubMedPubMedCentralGoogle Scholar
  51. Fatchiyah F, Hardiyanti F, Widodo N (2015) Selective inhibition on RAGE-binding AGEs required by bioactive peptide alpha-S2 case in protein from goat Ethawah breed milk: study of biological modeling. Acta Inform Med 23:90–96CrossRefPubMedPubMedCentralGoogle Scholar
  52. Ferrucci L, Guralnik JM, Woodman RC, Bandinelli S, Lauretani F, Corsi AM, Chaves PHM, Ershler WB, Longo DL (2005a) Proinflammatory state and circulating erythropoietin in persons with and without anemia. Am J Med 118:1288CrossRefPubMedGoogle Scholar
  53. Ferrucci L, Corsi A, Lauretani F, Bandinelli S, Bartali B, Taub DD, Guralnik JM, Longo DL (2005b) The origins of age-related proinflammatory state. Blood 105:2294–2299CrossRefPubMedGoogle Scholar
  54. Forbes JM, Cooper ME, Oldfield MD, Thomas MC (2003) Role of advanced glycation end products in diabetic nephropathy. J Am Soc Nephrol JASN 14:S254–S258CrossRefPubMedGoogle Scholar
  55. Franceschi C, Campisi J (2014) Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol Ser A 69:S4–S9CrossRefGoogle Scholar
  56. Franceschi C, Bonafè M, Valensin S, Olivieri F, De Luca M, Ottaviani E, De Benedictis G (2000) Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci 908:244–254CrossRefPubMedGoogle Scholar
  57. Franceschi C, Garagnani P, Vitale G, Capri M, Salvioli S (2017) Inflammaging and ‘Garb-aging’. Trends Endocrinol Metab 28:199–212CrossRefPubMedGoogle Scholar
  58. Franchi L, Muñoz-Planillo R, Núñez G (2012) Sensing and reacting to microbes through the inflammasomes. Nat Immunol 13:325–332CrossRefPubMedPubMedCentralGoogle Scholar
  59. Fransen F, van Beek AA, Borghuis T, Aidy SE, Hugenholtz F, van der Gaast-de Jongh C, Savelkoul HFJ, De Jonge MI, Boekschoten MV, Smidt H et al (2017) Aged gut microbiota contributes to systemical inflammaging after transfer to germ-free mice. Front Immunol 8:1385CrossRefPubMedPubMedCentralGoogle Scholar
  60. Fukami K, Yamagishi S-I, Okuda S (2014) Role of AGEs-RAGE system in cardiovascular disease. Curr Pharm Des 20:2395–2402CrossRefPubMedGoogle Scholar
  61. Fulop T, Larbi A, Dupuis G, Le Page A, Frost EH, Cohen AA, Witkowski JM, Franceschi C (2018) Immunosenescence and inflamm-aging as two sides of the same coin: friends or foes?. Front, Immunol, p 8Google Scholar
  62. Gao ZQ, Yang C, Wang YY, Wang P, Chen HL, Zhang XD, Liu R, Li WL, Qin XJ, Liang X et al (2008) RAGE upregulation and nuclear factor-kappaB activation associated with ageing rat cardiomyocyte dysfunction. Gen Physiol Biophys 27:152–158PubMedGoogle Scholar
  63. Gardella S, Andrei C, Ferrera D, Lotti LV, Torrisi MR, Bianchi ME, Rubartelli A (2002) The nuclear protein HMGB1 is secreted by monocytes via a non-classical, vesicle-mediated secretory pathway. EMBO Rep 3:995–1001CrossRefPubMedPubMedCentralGoogle Scholar
  64. Gerli R, Monti D, Bistoni O, Mazzone AM, Peri G, Cossarizza A, Di Gioacchino M, Cesarotti ME, Doni A, Mantovani A et al (2000) Chemokines, sTNF-Rs and sCD30 serum levels in healthy aged people and centenarians. Mech Ageing Dev 121:37–46CrossRefPubMedGoogle Scholar
  65. Geroldi D, Falcone C, Minoretti P, Emanuele E, Arra M, D’Angelo A (2006) High levels of soluble receptor for advanced glycation end products may be a marker of extreme longevity in humans. J Am Geriatr Soc 54:1149–1150CrossRefPubMedGoogle Scholar
  66. Ghidoni R, Benussi L, Glionna M, Franzoni M, Geroldi D, Emanuele E, Binetti G (2008) Decreased plasma levels of soluble receptor for advanced glycation end products in mild cognitive impairment. J Neural Transm 1996(115):1047–1050CrossRefGoogle Scholar
  67. Glenner GG, Wong CW (1984) Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 120:885–890CrossRefPubMedGoogle Scholar
  68. Goldin A, Beckman JA, Schmidt AM, Creager MA (2006) Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation 114:597–605CrossRefPubMedGoogle Scholar
  69. Grossin N, Auger F, Niquet-Leridon C, Durieux N, Montaigne D, Schmidt AM, Susen S, Jacolot P, Beuscart J-B, Tessier FJ et al (2015) Dietary CML-enriched protein induces functional arterial aging in a RAGE-dependent manner in mice. Mol Nutr Food Res 59:927–938CrossRefPubMedGoogle Scholar
  70. Gu Q, Wang B, Zhang X-F, Ma Y-P, Liu J-D, Wang X-Z (2014) Contribution of receptor for advanced glycation end products to vasculature-protecting effects of exercise training in aged rats. Eur J Pharmacol 741:186–194CrossRefPubMedGoogle Scholar
  71. Guo ZJ, Niu HX, Hou FF, Zhang L, Fu N, Nagai R, Lu X, Chen BH, Shan YX, Tian JW et al (2008) Advanced oxidation protein products activate vascular endothelial cells via a RAGE-mediated signaling pathway. Antioxid Redox Signal 10:1699–1712CrossRefPubMedGoogle Scholar
  72. Gursky O (2014) Hot spots in apolipoprotein A-II misfolding and amyloidosis in mice and men. FEBS Lett 588:845–850CrossRefPubMedPubMedCentralGoogle Scholar
  73. Hallam KM, Li Q, Ananthakrishnan R, Kalea A, Zou YS, Vedantham S, Schmidt AM, Yan SF, Ramasamy R (2010) Aldose Reductase and AGE–RAGE pathways: central roles in the pathogenesis of vascular dysfunction in aging rats. Aging Cell 9:776–784CrossRefPubMedPubMedCentralGoogle Scholar
  74. Harris HE, Andersson U (2004) Mini-review: the nuclear protein HMGB1 as a proinflammatory mediator. Eur J Immunol 34:1503–1512CrossRefGoogle Scholar
  75. Hauptmann G, Bahram S (2004) Genetics of the central MHC. Curr Opin Immunol 16:668–672CrossRefPubMedGoogle Scholar
  76. He Q, Liang CH, Lippard SJ (2000) Steroid hormones induce HMG1 overexpression and sensitize breast cancer cells to cisplatin and carboplatin. Proc Natl Acad Sci USA 97:5768–5772CrossRefPubMedGoogle Scholar
  77. He M, Kubo H, Morimoto K, Fujino N, Suzuki T, Takahasi T, Yamada M, Yamaya M, Maekawa T, Yamamoto Y et al (2011) Receptor for advanced glycation end products binds to phosphatidylserine and assists in the clearance of apoptotic cells. EMBO Rep 12:358–364CrossRefPubMedPubMedCentralGoogle Scholar
  78. Hearps AC, Martin GE, Angelovich TA, Cheng W-J, Maisa A, Landay AL, Jaworowski A, Crowe SM (2012) Aging is associated with chronic innate immune activation and dysregulation of monocyte phenotype and function. Aging Cell 11:867–875CrossRefPubMedGoogle Scholar
  79. Higuchi K, Kitagawa K, Naiki H, Hanada K, Hosokawa M, Takeda T (1991) Polymorphism of apolipoprotein A-II (apoA-II) among inbred strains of mice. Relationship between the molecular type of apoA-II and mouse senile amyloidosis. Biochem J 279(2):427–433CrossRefPubMedPubMedCentralGoogle Scholar
  80. Hofmann MA, Drury S, Fu C, Qu W, Taguchi A, Lu Y, Avila C, Kambham N, Bierhaus A, Nawroth P et al (1999) RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides. Cell 97:889–901CrossRefPubMedGoogle Scholar
  81. Hopkins MJ, Macfarlane GT (2002) Changes in predominant bacterial populations in human faeces with age and with Clostridium difficile infection. J Med Microbiol 51:448–454CrossRefPubMedGoogle Scholar
  82. Hopkins MJ, Sharp R, Macfarlane GT (2001) Age and disease related changes in intestinal bacterial populations assessed by cell culture, 16S rRNA abundance, and community cellular fatty acid profiles. Gut 48:198–205CrossRefPubMedPubMedCentralGoogle Scholar
  83. Hori O, Brett J, Slattery T, Cao R, Zhang J, Chen JX, Nagashima M, Lundh ER, Vijay S, Nitecki D (1995) The receptor for advanced glycation end products (RAGE) is a cellular binding site for amphoterin. Mediation of neurite outgrowth and co-expression of rage and amphoterin in the developing nervous system. J Biol Chem 270:25752–25761CrossRefPubMedGoogle Scholar
  84. Howes KA, Liu Y, Dunaief JL, Milam A, Frederick JM, Marks A, Baehr W (2004) Receptor for advanced glycation end products and age-related macular degeneration. Invest Ophthalmol Vis Sci 45:3713–3720CrossRefPubMedGoogle Scholar
  85. Huang JS, Guh JY, Chen HC, Hung WC, Lai YH, Chuang LY (2001) Role of receptor for advanced glycation end-product (RAGE) and the JAK/STAT-signaling pathway in AGE-induced collagen production in NRK-49F cells. J Cell Biochem 81:102–113CrossRefPubMedGoogle Scholar
  86. Hudson BI, Carter AM, Harja E, Kalea AZ, Arriero M, Yang H, Grant PJ, Schmidt AM (2008a) Identification, classification, and expression of RAGE gene splice variants. FASEB J 22:1572–1580CrossRefPubMedGoogle Scholar
  87. Hudson BI, Kalea AZ, Del Mar Arriero M, Harja E, Boulanger E, D’Agati V, Schmidt AM (2008b) Interaction of the RAGE cytoplasmic domain with diaphanous-1 is required for ligand-stimulated cellular migration through activation of Rac1 and Cdc42. J Biol Chem 283:34457–34468CrossRefPubMedPubMedCentralGoogle Scholar
  88. Iannuzzi C, Irace G, Sirangelo I (2014) Differential effects of glycation on protein aggregation and amyloid formation. Front Mol Biosci 1:9CrossRefPubMedPubMedCentralGoogle Scholar
  89. Ito H, Fujita K, Tagawa K, Chen X, Homma H, Sasabe T, Shimizu J, Shimizu S, Tamura T, Muramatsu S et al (2015) HMGB1 facilitates repair of mitochondrial DNA damage and extends the lifespan of mutant ataxin-1 knock-in mice. EMBO Mol Med 7:78–101CrossRefPubMedGoogle Scholar
  90. Ivanov A, Pawlikowski J, Manoharan I, van Tuyn J, Nelson DM, Rai TS, Shah PP, Hewitt G, Korolchuk VI, Passos JF et al (2013) Lysosome-mediated processing of chromatin in senescence. J Cell Biol 202:129–143CrossRefPubMedPubMedCentralGoogle Scholar
  91. Jastroch M, Divakaruni AS, Mookerjee S, Treberg JR, Brand MD (2010) Mitochondrial proton and electron leaks. Essays Biochem 47:53–67CrossRefPubMedPubMedCentralGoogle Scholar
  92. Jeon OH, David N, Campisi J, Elisseeff JH (2018) Senescent cells and osteoarthritis: a painful connection. J Clin Invest 128:1229–1237CrossRefPubMedPubMedCentralGoogle Scholar
  93. Jules J, Maiguel D, Hudson BI (2013) Alternative splicing of the RAGE cytoplasmic domain regulates cell signaling and function. PLoS ONE 8:e78267CrossRefPubMedPubMedCentralGoogle Scholar
  94. Jurk D, Wilson C, Passos JF, Oakley F, Correia-Melo C, Greaves L, Saretzki G, Fox C, Lawless C, Anderson R et al (2014) Chronic inflammation induces telomere dysfunction and accelerates ageing in mice. Nat Commun 5:4172CrossRefGoogle Scholar
  95. Kalea AZ, Reiniger N, Yang H, Arriero M, Schmidt AM, Hudson BI (2009) Alternative splicing of the murine receptor for advanced glycation end-products (RAGE) gene. FASEB J 23:1766–1774CrossRefPubMedPubMedCentralGoogle Scholar
  96. Kang P, Tian C, Jia C (2012) Association of RAGE gene polymorphisms with type 2 diabetes mellitus, diabetic retinopathy and diabetic nephropathy. Gene 500:1–9CrossRefPubMedGoogle Scholar
  97. Kang R, Chen R, Xie M, Cao L, Lotze MT, Tang D, Zeh HJ (2016) The receptor for advanced glycation endproducts (RAGE) activates the AIM2 inflammasome in acute pancreatitis. J Immunol Baltim Md 1950(196):4331–4337Google Scholar
  98. Kaufmann SHE, Dorhoi A (2016) Molecular determinants in phagocyte-bacteria interactions. Immunity 44:476–491CrossRefPubMedGoogle Scholar
  99. Kennedy BK, Berger SL, Brunet A, Campisi J, Cuervo AM, Epel ES, Franceschi C, Lithgow GJ, Morimoto RI, Pessin JE et al (2014a) Geroscience. Cell 159:709–713CrossRefPubMedPubMedCentralGoogle Scholar
  100. Kennedy BK, Berger SL, Brunet A, Campisi J, Cuervo AM, Epel ES, Franceschi C, Lithgow GJ, Morimoto RI, Pessin JE et al (2014b) Aging: a common driver of chronic diseases and a target for novel interventions. Cell 159:709–713CrossRefPubMedPubMedCentralGoogle Scholar
  101. Keri KC, Samji NS, Blumenthal S (2018) Diabetic nephropathy: newer therapeutic perspectives. J Community Hosp Intern Med Perspect 8:200–207CrossRefPubMedPubMedCentralGoogle Scholar
  102. Kierdorf K, Fritz G (2013) RAGE regulation and signaling in inflammation and beyond. J Leukoc Biol 94:55–68CrossRefPubMedGoogle Scholar
  103. Kim H-R, Won SJ, Fabian C, Kang M-G, Szardenings M, Shin M-G (2015) Mitochondrial DNA aberrations and pathophysiological implications in hematopoietic diseases, chronic inflammatory diseases, and cancers. Ann Lab Med 35:1–14CrossRefPubMedGoogle Scholar
  104. Kim EJ, Park SY, Baek SE, Jang MA, Lee WS, Bae SS, Kim K, Kim CD (2018) HMGB1 increases IL-1β production in vascular smooth muscle cells via NLRP3 inflammasome. Front Physiol 9:313CrossRefPubMedPubMedCentralGoogle Scholar
  105. Kislinger T, Fu C, Huber B, Qu W, Taguchi A, Du Yan S, Hofmann M, Yan SF, Pischetsrieder M, Stern D et al (1999) N(epsilon)-(carboxymethyl)lysine adducts of proteins are ligands for receptor for advanced glycation end products that activate cell signaling pathways and modulate gene expression. J Biol Chem 274:31740–31749CrossRefPubMedGoogle Scholar
  106. Kitagawa K, Wang J, Mastushita T, Kogishi K, Hosokawa M, Fu X, Guo Z, Mori M, Higuchi K (2003) Polymorphisms of mouse apolipoprotein A-II: seven alleles found among 41 inbred strains of mice. Amyloid 10:207–214CrossRefPubMedGoogle Scholar
  107. Kuhla A, Hettwer C, Menger MD, Vollmar B (2010) Oxidative stress-associated rise of hepatic protein glycation increases inflammatory liver injury in uncoupling protein-2 deficient mice. Lab. Investig. J. Tech. Methods Pathol. 90:1189–1198CrossRefGoogle Scholar
  108. Kuhla A, Hauke M, Sempert K, Vollmar B, Zechner D (2013) Senescence-dependent impact of anti-RAGE antibody on endotoxemic liver failure. Age 35:2153–2163CrossRefPubMedPubMedCentralGoogle Scholar
  109. Kumar V, Fleming T, Terjung S, Gorzelanny C, Gebhardt C, Agrawal R, Mall MA, Ranzinger J, Zeier M, Madhusudhan T et al (2017) Homeostatic nuclear RAGE-ATM interaction is essential for efficient DNA repair. Nucleic Acids Res 45:10595–10613CrossRefPubMedPubMedCentralGoogle Scholar
  110. Laforge M, Rodrigues V, Silvestre R, Gautier C, Weil R, Corti O, Estaquier J (2016) NF-κB pathway controls mitochondrial dynamics. Cell Death Differ 23:89–98CrossRefPubMedGoogle Scholar
  111. Lange SS, Vasquez KM (2009) HMGB1: the jack-of-all-trades protein is a master DNA repair mechanic. Mol Carcinog 48:571–580CrossRefPubMedPubMedCentralGoogle Scholar
  112. Lange SS, Mitchell DL, Vasquez KM (2008) High mobility group protein B1 enhances DNA repair and chromatin modification after DNA damage. Proc Natl Acad Sci USA 105:10320–10325CrossRefPubMedGoogle Scholar
  113. Larkin DJ, Kartchner JZ, Doxey AS, Hollis WR, Rees JL, Wilhelm SK, Draper CS, Peterson DM, Jackson GG, Ingersoll C et al (2013) Inflammatory markers associated with osteoarthritis after destabilization surgery in young mice with and without receptor for advanced glycation end-products (RAGE). Front Physiol 4:121CrossRefPubMedPubMedCentralGoogle Scholar
  114. Leclerc E, Vetter SW (2015) The role of S100 proteins and their receptor RAGE in pancreatic cancer. Biochim Biophys Acta 1852:2706–2711CrossRefPubMedPubMedCentralGoogle Scholar
  115. Leclerc E, Fritz G, Vetter SW, Heizmann CW (2009) Binding of S100 proteins to RAGE: an update. Biochim Biophys Acta 1793:993–1007CrossRefPubMedGoogle Scholar
  116. Li J, Schmidt AM (1997) Characterization and functional analysis of the promoter of RAGE, the receptor for advanced glycation end products. J Biol Chem 272:16498–16506CrossRefPubMedGoogle Scholar
  117. Li L, Liu X, Glassman AB, Keating MJ, Stros M, Plunkett W, Yang L-Y (1997) Fludarabine triphosphate inhibits nucleotide excision repair of cisplatin-induced DNA adducts in vitro. Cancer Res 57:1487–1494PubMedGoogle Scholar
  118. Li Y, Wu R, Tian Y, Yu M, Tang Y, Cheng H, Tian Z (2015) RAGE/NF-κB signaling mediates lipopolysaccharide induced acute lung injury in neonate rat model. Int J Clin Exp Med 8:13371–13376PubMedPubMedCentralGoogle Scholar
  119. Liliensiek B, Weigand MA, Bierhaus A, Nicklas W, Kasper M, Hofer S, Plachky J, Gröne H-J, Kurschus FC, Schmidt AM et al (2004) Receptor for advanced glycation end products (RAGE) regulates sepsis but not the adaptive immune response. J Clin Invest 113:1641–1650CrossRefPubMedPubMedCentralGoogle Scholar
  120. Lin L (2006) RAGE on the Toll Road? Cell Mol Immunol 3:351–358PubMedGoogle Scholar
  121. Lin L, Park S, Lakatta EG (2009) RAGE signaling in inflammation and arterial aging. Front Biosci 14:1403–1413CrossRefPubMedCentralGoogle Scholar
  122. Liu Y, Liang C, Liu X, Liao B, Pan X, Ren Y, Fan M, Li M, He Z, Wu J et al (2010) AGEs increased migration and inflammatory responses of adventitial fibroblasts via RAGE, MAPK and NF-kappaB pathways. Atherosclerosis 208:34–42CrossRefPubMedGoogle Scholar
  123. Liu J, Huang K, Cai G-Y, Chen X-M, Yang J-R, Lin L-R, Yang J, Huo B-G, Zhan J, He Y-N (2014) Receptor for advanced glycation end-products promotes premature senescence of proximal tubular epithelial cells via activation of endoplasmic reticulum stress-dependent p21 signaling. Cell Signal 26:110–121CrossRefPubMedGoogle Scholar
  124. Lo M-C, Chen M-H, Lee W-S, Lu C-I, Chang C-R, Kao S-H, Lee H-M (2015) Nε-(carboxymethyl) lysine-induced mitochondrial fission and mitophagy cause decreased insulin secretion from β-cells. Am J Physiol Endocrinol Metab 309:E829–E839CrossRefPubMedGoogle Scholar
  125. Loeser RF, Yammani RR, Carlson CS, Chen H, Cole A, Im H-J, Bursch LS, Yan SD (2005) Articular chondrocytes express the receptor for advanced glycation end products: potential role in osteoarthritis. Arthritis Rheum 52:2376–2385CrossRefPubMedPubMedCentralGoogle Scholar
  126. Lopetuso LR, Scaldaferri F, Petito V, Gasbarrini A (2013) Commensal Clostridia: leading players in the maintenance of gut homeostasis. Gut Pathog 5:23CrossRefPubMedPubMedCentralGoogle Scholar
  127. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G (2013) The hallmarks of aging. Cell 153:1194–1217CrossRefPubMedPubMedCentralGoogle Scholar
  128. Ma W, Rai V, Hudson BI, Song F, Schmidt AM, Barile GR (2012) RAGE binds C1q and enhances C1q-mediated phagocytosis. Cell Immunol 274:72–82CrossRefPubMedGoogle Scholar
  129. Magna M, Pisetsky DS (2014) The role of HMGB1 in the pathogenesis of inflammatory and autoimmune diseases. Mol Med 20:138–146CrossRefPubMedPubMedCentralGoogle Scholar
  130. Maillard-Lefebvre H, Boulanger E, Daroux M, Gaxatte C, Hudson BI, Lambert M (2009) Soluble receptor for advanced glycation end products: a new biomarker in diagnosis and prognosis of chronic inflammatory diseases. Rheumatol Oxf Engl 48:1190–1196CrossRefGoogle Scholar
  131. Malaquin N, Martinez A, Rodier F (2016) Keeping the senescence secretome under control: molecular reins on the senescence-associated secretory phenotype. Exp Gerontol 82:39–49CrossRefPubMedGoogle Scholar
  132. Man SM, Kanneganti T-D (2015) Regulation of inflammasome activation. Immunol Rev 265:6–21CrossRefPubMedPubMedCentralGoogle Scholar
  133. Manfredi AA, Capobianco A, Esposito A, De Cobelli F, Canu T, Monno A, Raucci A, Sanvito F, Doglioni C, Nawroth PP et al (2008) Maturing dendritic cells depend on RAGE for in vivo homing to lymph nodes. J Immunol Baltim Md 1950(180):2270–2275Google Scholar
  134. Manigrasso MB, Pan J, Rai V, Zhang J, Reverdatto S, Quadri N, DeVita RJ, Ramasamy R, Shekhtman A, Schmidt AM (2016) Small molecule inhibition of ligand-stimulated RAGE-DIAPH1 signal transduction. Sci Rep 6:22450CrossRefPubMedPubMedCentralGoogle Scholar
  135. Mankan AK, Schmidt T, Chauhan D, Goldeck M, Höning K, Gaidt M, Kubarenko AV, Andreeva L, Hopfner K-P, Hornung V (2014) Cytosolic RNA:DNA hybrids activate the cGAS–STING axis. EMBO J 33:2937–2946CrossRefPubMedPubMedCentralGoogle Scholar
  136. Mao YX, Cai WJ, Sun XY, Dai PP, Li XM, Wang Q, Huang XL, He B, Wang PP, Wu G et al (2018) RAGE-dependent mitochondria pathway: a novel target of silibinin against apoptosis of osteoblastic cells induced by advanced glycation end products. Cell Death Dis 9:674CrossRefPubMedPubMedCentralGoogle Scholar
  137. Mariani E, Cattini L, Neri S, Malavolta M, Mocchegiani E, Ravaglia G, Facchini A (2006) Simultaneous evaluation of circulating chemokine and cytokine profiles in elderly subjects by multiplex technology: relationship with zinc status. Biogerontology 7:449–459CrossRefPubMedGoogle Scholar
  138. Masters PM, Bada JL, Zigler JS (1977) Aspartic acid racemisation in the human lens during ageing and in cataract formation. Nature 268:71–73CrossRefPubMedGoogle Scholar
  139. Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K (1985a) Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci USA 82:4245–4249CrossRefPubMedGoogle Scholar
  140. Masters CL, Multhaup G, Simms G, Pottgiesser J, Martins RN, Beyreuther K (1985b) Neuronal origin of a cerebral amyloid: neurofibrillary tangles of Alzheimer’s disease contain the same protein as the amyloid of plaque cores and blood vessels. EMBO J 4:2757–2763CrossRefPubMedPubMedCentralGoogle Scholar
  141. Minciullo PL, Catalano A, Mandraffino G, Casciaro M, Crucitti A, Maltese G, Morabito N, Lasco A, Gangemi S, Basile G (2016) Inflammaging and anti-inflammaging: the role of cytokines in extreme longevity. Arch Immunol Ther Exp (Warsz) 64:111–126CrossRefGoogle Scholar
  142. Misur I, Zarković K, Barada A, Batelja L, Milicević Z, Turk Z (2004) Advanced glycation endproducts in peripheral nerve in type 2 diabetes with neuropathy. Acta Diabetol 41:158–166CrossRefPubMedGoogle Scholar
  143. Monnier VM, Cerami A (1981) Nonenzymatic browning in vivo: possible process for aging of long-lived proteins. Science 211:491–493CrossRefPubMedGoogle Scholar
  144. Morizane R, Monkawa T, Konishi K, Hashiguchi A, Ueda M, Ando Y, Tokuyama H, Hayashi K, Hayashi M, Itoh H (2011) Renal amyloidosis caused by apolipoprotein A-II without a genetic mutation in the coding sequence. Clin Exp Nephrol 15:774–779CrossRefPubMedGoogle Scholar
  145. Morrisette-Thomas V, Cohen AA, Fülöp T, Riesco É, Legault V, Li Q, Milot E, Dusseault-Bélanger F, Ferrucci L (2014) Inflamm-aging does not simply reflect increases in pro-inflammatory markers. Mech Ageing Dev 139:49–57CrossRefPubMedPubMedCentralGoogle Scholar
  146. Moser B, Desai DD, Downie MP, Chen Y, Yan SF, Herold K, Schmidt AM, Clynes R (2007) Receptor for advanced glycation end products expression on T cells contributes to antigen-specific cellular expansion in vivo. J Immunol Baltim Md 1950(179):8051–8058Google Scholar
  147. Most P, Seifert H, Gao E, Funakoshi H, Völkers M, Heierhorst J, Remppis A, Pleger ST, DeGeorge BR, Eckhart AD et al (2006) Cardiac S100A1 protein levels determine contractile performance and propensity toward heart failure after myocardial infarction. Circulation 114:1258–1268CrossRefPubMedGoogle Scholar
  148. Narumi K, Miyakawa R, Ueda R, Hashimoto H, Yamamoto Y, Yoshida T, Aoki K (2015) Proinflammatory proteins S100A8/S100A9 activate NK cells via interaction with RAGE. J Immunol Baltim Md 1950(194):5539–5548Google Scholar
  149. Navarrete Santos A, Jacobs K, Simm A, Glaubitz N, Horstkorte R, Hofmann B (2017) Dicarbonyls induce senescence of human vascular endothelial cells. Mech Ageing Dev 166:24–32CrossRefPubMedGoogle Scholar
  150. Neeper M, Schmidt AM, Brett J, Yan SD, Wang F, Pan YC, Elliston K, Stern D, Shaw A (1992) Cloning and expression of a cell surface receptor for advanced glycosylation end products of proteins. J Biol Chem 267:14998–15004PubMedGoogle Scholar
  151. Neviere R, Yu Y, Wang L, Tessier F, Boulanger E (2016) Implication of advanced glycation end products (Ages) and their receptor (Rage) on myocardial contractile and mitochondrial functions. Glycoconj J 33:607–617CrossRefPubMedGoogle Scholar
  152. Nguyen THO, Sant S, Bird NL, Grant EJ, Clemens EB, Koutsakos M, Valkenburg SA, Gras S, Lappas M, Jaworowski A et al (2018) Perturbed CD8+ T cell immunity across universal influenza epitopes in the elderly. J Leukoc Biol 103:321–339PubMedGoogle Scholar
  153. Oczypok EA, Perkins TN, Oury TD (2017) All the “RAGE” in lung disease: the receptor for advanced glycation endproducts (RAGE) is a major mediator of pulmonary inflammatory responses. Paediatr Respir Rev 23:40–49PubMedPubMedCentralGoogle Scholar
  154. Olejarz W, Łacheta D, Głuszko A, Migacz E, Kukwa W, Szczepański MJ, Tomaszewski P, Nowicka G (2018) RAGE and TLRs as key targets for antiatherosclerotic therapy. Biomed Res Int.  https://doi.org/10.1155/2018/7675286 CrossRefPubMedPubMedCentralGoogle Scholar
  155. Oliveira JB, Soares AASM, Sposito AC (2018) Inflammatory response during myocardial infarction. Adv Clin Chem 84:39–79CrossRefPubMedGoogle Scholar
  156. Ostendorp T, Leclerc E, Galichet A, Koch M, Demling N, Weigle B, Heizmann CW, Kroneck PMH, Fritz G (2007) Structural and functional insights into RAGE activation by multimeric S100B. EMBO J 26:3868–3878CrossRefPubMedPubMedCentralGoogle Scholar
  157. Park H, Adsit FG, Boyington JC (2010) The 1.5 Å crystal structure of human receptor for advanced glycation endproducts (RAGE) ectodomains reveals unique features determining ligand binding. J Biol Chem 285:40762–40770CrossRefPubMedPubMedCentralGoogle Scholar
  158. Park S, Yoon S-J, Tae H-J, Shim CY (2011) RAGE and cardiovascular disease. Front Biosci Landmark Ed 16:486–497CrossRefPubMedGoogle Scholar
  159. Pawelec G (2017) Immunosenescence and cancer. Biogerontology 18:717–721CrossRefPubMedGoogle Scholar
  160. Pelucchi C, Galeone C, Levi F, Negri E, Franceschi S, Talamini R, Bosetti C, Giacosa A, La Vecchia C (2006) Dietary acrylamide and human cancer. Int J Cancer 118:467–471CrossRefPubMedGoogle Scholar
  161. Peng Q, Li K, Sacks SH, Zhou W (2009) The role of anaphylatoxins C3a and C5a in regulating innate and adaptive immune responses. Inflamm Allergy Drug Targets 8:236–246CrossRefPubMedGoogle Scholar
  162. Peng Y, Park H-S, Tang LA, Horwitz N, Lin L (2019) Generation of sRAGEhigh transgenic mice to study inflammaging. Front Biosci Landmark Ed 24:555–563CrossRefPubMedGoogle Scholar
  163. Pettersson-Fernholm K, Forsblom C, Hudson BI, Perola M, Grant PJ, Groop P-H (2003) The functional —374 T/A RAGE gene polymorphism is associated with proteinuria and cardiovascular disease in type 1 diabetic patients. Diabetes 52:891–894CrossRefPubMedGoogle Scholar
  164. Porcel JM, Ordi J, Castro-Salomo A, Vilardell M, Rodrigo MJ, Gene T, Warburton F, Kraus M, Vergani D (1995) The value of complement activation products in the assessment of systemic lupus erythematosus flares. Clin Immunol Immunopathol 74:283–288CrossRefPubMedGoogle Scholar
  165. Prusiner SB (1982) Novel proteinaceous infectious particles cause scrapie. Science 216:136–144CrossRefPubMedGoogle Scholar
  166. Prusiner SB (1991) Molecular biology of prion diseases. Science 252:1515–1522CrossRefPubMedGoogle Scholar
  167. Rai V, Maldonado AY, Burz DS, Reverdatto S, Yan SF, Schmidt AM, Shekhtman A (2012a) Signal transduction in receptor for advanced glycation end products (RAGE): solution structure of C-terminal rage (ctRAGE) and its binding to mDia1. J Biol Chem 287:5133–5144CrossRefPubMedGoogle Scholar
  168. Rai V, Touré F, Chitayat S, Pei R, Song F, Li Q, Zhang J, Rosario R, Ramasamy R, Chazin WJ et al (2012b) Lysophosphatidic acid targets vascular and oncogenic pathways via RAGE signaling. J Exp Med 209:2339–2350CrossRefPubMedPubMedCentralGoogle Scholar
  169. Rainone V, Schneider L, Saulle I, Ricci C, Biasin M, Al-Daghri NM, Giani E, Zuccotti GV, Clerici M, Trabattoni D (2016) Upregulation of inflammasome activity and increased gut permeability are associated with obesity in children and adolescents. Int J Obes 2005(40):1026–1033CrossRefGoogle Scholar
  170. Rambaran RN, Serpell LC (2008) Amyloid fibrils. Prion 2:112–117CrossRefPubMedPubMedCentralGoogle Scholar
  171. Rampelli S, Candela M, Turroni S, Biagi E, Collino S, Franceschi C, O’Toole PW, Brigidi P (2013) Functional metagenomic profiling of intestinal microbiome in extreme ageing. Aging 5:902–912CrossRefPubMedPubMedCentralGoogle Scholar
  172. Raucci A, Cugusi S, Antonelli A, Barabino SM, Monti L, Bierhaus A, Reiss K, Saftig P, Bianchi ME (2008) A soluble form of the receptor for advanced glycation endproducts (RAGE) is produced by proteolytic cleavage of the membrane-bound form by the sheddase a disintegrin and metalloprotease 10 (ADAM10). FASEB J Off Publ Fed Am Soc Exp Biol 22:3716–3727Google Scholar
  173. Ray R, Juranek JK, Rai V (2016) RAGE axis in neuroinflammation, neurodegeneration and its emerging role in the pathogenesis of amyotrophic lateral sclerosis. Neurosci Biobehav Rev 62:48–55CrossRefPubMedGoogle Scholar
  174. Rivera A, Siracusa MC, Yap GS, Gause WC (2016) Innate cell communication kick-starts pathogen-specific immunity. Nat Immunol 17:356–363CrossRefPubMedPubMedCentralGoogle Scholar
  175. Ruan BH, Li X, Winkler AR, Cunningham KM, Kuai J, Greco RM, Nocka KH, Fitz LJ, Wright JF, Pittman DD et al (2010) Complement C3a, CpG oligos, and DNA/C3a complex stimulate IFN-α production in a receptor for advanced glycation end product-dependent manner. J Immunol Baltim Md 1950(185):4213–4222Google Scholar
  176. Sakaguchi M, Murata H, Yamamoto K, Ono T, Sakaguchi Y, Motoyama A, Hibino T, Kataoka K, Huh N (2011) TIRAP, an adaptor protein for TLR2/4, transduces a signal from RAGE phosphorylated upon ligand binding. PLoS ONE 6(8):e23132CrossRefPubMedPubMedCentralGoogle Scholar
  177. Scaffidi P, Misteli T, Bianchi ME (2002) Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature 418:191–195CrossRefPubMedPubMedCentralGoogle Scholar
  178. Schmidt AM (2017) RAGE and implications for the pathogenesis and treatment of cardiometabolic disorders—spotlight on the macrophage. Arterioscler Thromb Vasc Biol 37:613–621CrossRefPubMedPubMedCentralGoogle Scholar
  179. Schmidt AM, Vianna M, Gerlach M, Brett J, Ryan J, Kao J, Esposito C, Hegarty H, Hurley W, Clauss M (1992) Isolation and characterization of two binding proteins for advanced glycosylation end products from bovine lung which are present on the endothelial cell surface. J Biol Chem 267:14987–14997PubMedGoogle Scholar
  180. Seidler S, Zimmermann HW, Bartneck M, Trautwein C, Tacke F (2010) Age-dependent alterations of monocyte subsets and monocyte-related chemokine pathways in healthy adults. BMC Immunol 11:30CrossRefPubMedPubMedCentralGoogle Scholar
  181. Sell DR, Lane MA, Johnson WA, Masoro EJ, Mock OB, Reiser KM, Fogarty JF, Cutler RG, Ingram DK, Roth GS et al (1996) Longevity and the genetic determination of collagen glycoxidation kinetics in mammalian senescence. Proc Natl Acad Sci USA 93:485–490CrossRefPubMedGoogle Scholar
  182. Sellier C, Boulanger E, Maladry F, Tessier FJ, Lorenzi R, Nevière R, Desreumaux P, Beuscart J-B, Puisieux F, Grossin N (2015) Acrylamide induces accelerated endothelial aging in a human cell model. Food Chem Toxicol Int J Publ Br Ind Biol Res Assoc 83:140–145CrossRefGoogle Scholar
  183. Senatus LM, Schmidt AM (2017) The AGE-RAGE axis: implications for age-associated arterial diseases. Front, Genet, p 8Google Scholar
  184. Serratos IN, Castellanos P, Pastor N, Millán-Pacheco C, Rembao D, Pérez-Montfort R, Cabrera N, Reyes-Espinosa F, Díaz-Garrido P, López-Macay A et al (2015) Modeling the Interaction between Quinolinate and the Receptor for Advanced Glycation End Products (RAGE): relevance for Early Neuropathological Processes. PLoS ONE 10(3):120221CrossRefGoogle Scholar
  185. Sessa L, Gatti E, Zeni F, Antonelli A, Catucci A, Koch M, Pompilio G, Fritz G, Raucci A, Bianchi ME (2014) The receptor for advanced glycation end-products (RAGE) is only present in mammals, and belongs to a family of cell adhesion molecules (CAMs). PLoS ONE 9:e86903CrossRefPubMedPubMedCentralGoogle Scholar
  186. Shahab U, Ahmad MK, Mahdi AA, Waseem M, Arif B, Moinuddin, Ahmad S (2018) The receptor for advanced glycation end products: a fuel to pancreatic cancer. Semin Cancer Biol 49:37–43CrossRefPubMedGoogle Scholar
  187. Shahzad K, Bock F, Dong W, Wang H, Kopf S, Kohli S, Al-Dabet MM, Ranjan S, Wolter J, Wacker C et al (2015) Nlrp3-inflammasome activation in non-myeloid-derived cells aggravates diabetic nephropathy. Kidney Int 87:74–84CrossRefPubMedGoogle Scholar
  188. Shen YJ, Le Bert N, Chitre AA, Koo CX, Nga XH, Ho SSW, Khatoo M, Tan NY, Ishii KJ, Gasser S (2015) Genome-derived cytosolic DNA mediates type I interferon-dependent rejection of B cell lymphoma cells. Cell Rep 11:460–473CrossRefPubMedGoogle Scholar
  189. Shimada K, Crother TR, Karlin J, Dagvadorj J, Chiba N, Chen S, Ramanujan VK, Wolf AJ, Vergnes L, Ojcius DM et al (2012) Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis. Immunity 36:401–414CrossRefPubMedPubMedCentralGoogle Scholar
  190. Shirasawa M, Fujiwara N, Hirabayashi S, Ohno H, Iida J, Makita K, Hata Y (2004) Receptor for advanced glycation end-products is a marker of type I lung alveolar cells. Genes Cells 9:165–174CrossRefPubMedGoogle Scholar
  191. Shuvaev VV, Laffont I, Serot JM, Fujii J, Taniguchi N, Siest G (2001) Increased protein glycation in cerebrospinal fluid of Alzheimer’s disease. Neurobiol Aging 22:397–402CrossRefPubMedGoogle Scholar
  192. Silverstein DM (2009) Inflammation in chronic kidney disease: role in the progression of renal and cardiovascular disease. Pediatr. Nephrol. Berl. Ger. 24:1445–1452CrossRefGoogle Scholar
  193. Simm A, Casselmann C, Schubert A, Hofmann S, Reimann A, Silber R-E (2004) Age associated changes of AGE-receptor expression: RAGE upregulation is associated with human heart dysfunction. Exp Gerontol 39:407–413CrossRefPubMedGoogle Scholar
  194. Somensi N, Brum PO, de Miranda Ramos V, Gasparotto J, Zanotto-Filho A, Rostirolla DC, da Silva Morrone M, Moreira JCF, Pens Gelain D (2017) Extracellular HSP70 activates ERK1/2, NF-kB and pro-inflammatory gene transcription through binding with RAGE in A549 human lung cancer cells. Cell Physiol Biochem Int J Exp Cell Physiol Biochem Pharmacol 42:2507–2522CrossRefGoogle Scholar
  195. Son M, Chung W-J, Oh S, Ahn H, Choi CH, Hong S, Park KY, Son KH, Byun K (2017) Age dependent accumulation patterns of advanced glycation end product receptor (RAGE) ligands and binding intensities between RAGE and its ligands differ in the liver, kidney, and skeletal muscle. Immun Ageing A 14:12CrossRefGoogle Scholar
  196. Song Y, Wang Y, Zhang Y, Geng W, Liu W, Gao Y, Li S, Wang K, Wu X, Kang L et al (2017) Advanced glycation end products regulate anabolic and catabolic activities via NLRP3-inflammasome activation in human nucleus pulposus cells. J Cell Mol Med 21:1373–1387CrossRefPubMedPubMedCentralGoogle Scholar
  197. Sorci G, Riuzzi F, Giambanco I, Donato R (2013) RAGE in tissue homeostasis, repair and regeneration. Biochim Biophys Acta 1833:101–109CrossRefPubMedGoogle Scholar
  198. Sousa MM, Yan SD, Stern D, Saraiva MJ (2000) Interaction of the receptor for advanced glycation end products (RAGE) with transthyretin triggers nuclear transcription factor kB (NF-kB) activation. Lab Invest 80:1101–1110CrossRefPubMedGoogle Scholar
  199. Sparvero LJ, Asafu-Adjei D, Kang R, Tang D, Amin N, Im J, Rutledge R, Lin B, Amoscato AA, Zeh HJ et al (2009) RAGE (receptor for advanced glycation endproducts), RAGE ligands, and their role in cancer and inflammation. J Transl Med 7:17CrossRefPubMedPubMedCentralGoogle Scholar
  200. Sugaya K, Fukagawa T, Matsumoto K, Mita K, Takahashi E, Ando A, Inoko H, Ikemura T (1994) Three genes in the human MHC class III region near the junction with the class II: gene for receptor of advanced glycosylation end products, PBX2 homeobox gene and a notch homolog, human counterpart of mouse mammary tumor gene int-3. Genomics 23:408–419CrossRefPubMedGoogle Scholar
  201. Sugimoto K, Yasujima M, Yagihashi S (2008) Role of advanced glycation end products in diabetic neuropathy. Curr Pharm Des 14:953–961CrossRefPubMedGoogle Scholar
  202. Sun X-H, Liu Y, Han Y, Wang J (2016) Expression and significance of high-mobility group protein B1 (HMGB1) and the receptor for advanced glycation end-product (RAGE) in knee osteoarthritis. Med Sci Monit Int Med J Exp Clin Res 22:2105–2112Google Scholar
  203. Suski JM, Lebiedzinska M, Bonora M, Pinton P, Duszynski J, Wieckowski MR (2012) Relation between mitochondrial membrane potential and ROS formation. Methods Mol Biol Clifton NJ 810:183–205CrossRefGoogle Scholar
  204. Tan ALY, Sourris KC, Harcourt BE, Thallas-Bonke V, Penfold S, Andrikopoulos S, Thomas MC, O’Brien RC, Bierhaus A, Cooper ME et al (2009) Disparate effects on renal and oxidative parameters following RAGE deletion, AGE accumulation inhibition, or dietary AGE control in experimental diabetic nephropathy. Am J Physiol Ren Physiol 298:F763–F770CrossRefGoogle Scholar
  205. Tanaka N, Yonekura H, Yamagishi S, Fujimori H, Yamamoto Y, Yamamoto H (2000) The receptor for advanced glycation end products is induced by the glycation products themselves and tumor necrosis factor-alpha through nuclear factor-kappa B, and by 17beta-estradiol through Sp-1 in human vascular endothelial cells. J Biol Chem 275:25781–25790CrossRefPubMedGoogle Scholar
  206. Teh BK, Yeo JG, Chern LM, Lu J (2011) C1q regulation of dendritic cell development from monocytes with distinct cytokine production and T cell stimulation. Mol Immunol 48:1128–1138CrossRefPubMedGoogle Scholar
  207. Teissier T, Quersin V, Gnemmi V, Daroux M, Howsam M, Delguste F, Lemoine C, Fradin C, Schmidt A-M, Cauffiez C et al (2019) Knockout of receptor for advanced glycation end-products attenuates age-related renal lesions. Aging Cell 18:e12850CrossRefPubMedPubMedCentralGoogle Scholar
  208. Tessier FJ, Niquet-Léridon C, Jacolot P, Jouquand C, Genin M, Schmidt A-M, Grossin N, Boulanger E (2016) Quantitative assessment of organ distribution of dietary protein-bound (13) C-labeled N(ɛ)-carboxymethyllysine after a chronic oral exposure in mice. Mol Nutr Food Res 60(11):2446–2456CrossRefPubMedGoogle Scholar
  209. Thankam FG, Roesch ZK, Dilisio MF, Radwan MM, Kovilam A, Gross RM, Agrawal DK (2018) Association of inflammatory responses and ECM disorganization with HMGB1 upregulation and NLRP3 inflammasome activation in the injured rotator cuff tendon. Sci Rep 8:8918CrossRefPubMedPubMedCentralGoogle Scholar
  210. Thevaranjan N, Puchta A, Schulz C, Naidoo A, Szamosi JC, Verschoor CP, Loukov D, Schenck LP, Jury J, Foley KP et al (2017) Age-associated microbial dysbiosis promotes intestinal permeability, systemic inflammation, and macrophage dysfunction. Cell Host Microbe 21:455.e4–466.e4CrossRefGoogle Scholar
  211. Thornalley PJ, Battah S, Ahmed N, Karachalias N, Agalou S, Babaei-Jadidi R, Dawnay A (2003) Quantitative screening of advanced glycation endproducts in cellular and extracellular proteins by tandem mass spectrometry. Biochem J 375:581–592CrossRefPubMedPubMedCentralGoogle Scholar
  212. Tian J, Avalos AM, Mao S-Y, Chen B, Senthil K, Wu H, Parroche P, Drabic S, Golenbock D, Sirois C et al (2007) Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE. Nat Immunol 8:487–496CrossRefPubMedGoogle Scholar
  213. Tran L, Greenwood-Van Meerveld B (2013) Age-associated remodeling of the intestinal epithelial barrier. J Gerontol A 68:1045–1056CrossRefGoogle Scholar
  214. Tsung A, Tohme S, Billiar TR (2014) High-mobility group box-1 in sterile inflammation. J Intern Med 276:425–443CrossRefPubMedGoogle Scholar
  215. Tulkens J, Vergauwen G, Van Deun J, Geeurickx E, Dhondt B, Lippens L, De Scheerder M-A, Miinalainen I, Rappu P, De Geest BG et al (2018) Increased levels of systemic LPS-positive bacterial extracellular vesicles in patients with intestinal barrier dysfunction. Gut.  https://doi.org/10.1136/gutjnl-2018-317726 CrossRefPubMedGoogle Scholar
  216. Tuppen HAL, Blakely EL, Turnbull DM, Taylor RW (2010) Mitochondrial DNA mutations and human disease. Biochim Biophys Acta 1797:113–128CrossRefPubMedGoogle Scholar
  217. Turner DP (2015) Advanced glycation end-products: a biological consequence of lifestyle contributing to cancer disparity. Cancer Res 75:1925–1929CrossRefPubMedPubMedCentralGoogle Scholar
  218. van Hout GPJ, Arslan F, Pasterkamp G, Hoefer IE (2016) Targeting danger-associated molecular patterns after myocardial infarction. Expert Opin Ther Targets 20:223–239CrossRefPubMedGoogle Scholar
  219. van Zoelen MAD, Schouten M, de Vos AF, Florquin S, Meijers JCM, Nawroth PP, Bierhaus A, van der Poll T (2009) The receptor for advanced glycation end products impairs host defense in pneumococcal pneumonia. J Immunol Baltim Md 1950(182):4349–4356Google Scholar
  220. van Zoelen MAD, Wieland CW, van der Windt GJW, Florquin S, Nawroth PP, Bierhaus A, van der Poll T (2012) Receptor for advanced glycation end products is protective during murine tuberculosis. Mol Immunol 52:183–189CrossRefPubMedGoogle Scholar
  221. Venereau E, Schiraldi M, Uguccioni M, Bianchi ME (2013) HMGB1 and leukocyte migration during trauma and sterile inflammation. Mol Immunol 55:76–82CrossRefPubMedGoogle Scholar
  222. Verzijl N, DeGroot J, Thorpe SR, Bank RA, Shaw JN, Lyons TJ, Bijlsma JW, Lafeber FP, Baynes JW, TeKoppele JM (2000) Effect of collagen turnover on the accumulation of advanced glycation end products. J Biol Chem 275:39027–39031CrossRefPubMedGoogle Scholar
  223. Wada R, Yagihashi S (2005) Role of advanced glycation end products and their receptors in development of diabetic neuropathy. Ann N Y Acad Sci 1043:598–604CrossRefPubMedGoogle Scholar
  224. Walton GE, van den Heuvel EGHM, Kosters MHW, Rastall RA, Tuohy KM, Gibson GR (2012) A randomised crossover study investigating the effects of galacto-oligosaccharides on the faecal microbiota in men and women over 50 years of age. Br J Nutr 107:1466–1475CrossRefPubMedGoogle Scholar
  225. Wang JQ, Jeelall YS, Ferguson LL, Horikawa K (2014) Toll-like receptors and cancer: MYD88 mutation and inflammation. Front, Immunol, p 5Google Scholar
  226. Wang J, Zeng J, Wang H, Ye S, Bi Y, Zhou Y, Li K, Zhou Y (2016) Genetic polymorphisms of RAGE and risk of ulcerative colitis in a Chinese population. Immunol Lett 170:88–94CrossRefPubMedGoogle Scholar
  227. Ward MS, Fortheringham AK, Cooper ME, Forbes JM (2013) Targeting advanced glycation endproducts and mitochondrial dysfunction in cardiovascular disease. Curr Opin Pharmacol 13:654–661CrossRefPubMedGoogle Scholar
  228. Wautier MP, Chappey O, Corda S, Stern DM, Schmidt AM, Wautier JL (2001) Activation of NADPH oxidase by AGE links oxidant stress to altered gene expression via RAGE. Am J Physiol Endocrinol Metab 280:E685–E694CrossRefPubMedGoogle Scholar
  229. Wendt TM, Tanji N, Guo J, Kislinger TR, Qu W, Lu Y, Bucciarelli LG, Rong LL, Moser B, Markowitz GS et al (2003) RAGE drives the development of glomerulosclerosis and implicates podocyte activation in the pathogenesis of diabetic nephropathy. Am J Pathol 162:1123–1137CrossRefPubMedPubMedCentralGoogle Scholar
  230. Wolf L, Herr C, Niederstraßer J, Beisswenger C, Bals R (2017) Receptor for advanced glycation endproducts (RAGE) maintains pulmonary structure and regulates the response to cigarette smoke. PLoS ONE 12:e0180092CrossRefPubMedPubMedCentralGoogle Scholar
  231. Xie J, Burz DS, He W, Bronstein IB, Lednev I, Shekhtman A (2007) Hexameric calgranulin C (S100A12) binds to the receptor for advanced glycated end products (RAGE) using symmetric hydrophobic target-binding patches. J Biol Chem 282:4218–4231CrossRefPubMedGoogle Scholar
  232. Xie J, Reverdatto S, Frolov A, Hoffmann R, Burz DS, Shekhtman A (2008) Structural basis for pattern recognition by the receptor for advanced glycation end products (RAGE). J Biol Chem 283:27255–27269CrossRefPubMedGoogle Scholar
  233. Xie J, Méndez JD, Méndez-Valenzuela V, Aguilar-Hernández MM (2013) Cellular signalling of the receptor for advanced glycation end products (RAGE). Cell Signal 25:2185–2197CrossRefPubMedGoogle Scholar
  234. Xu M, Bradley EW, Weivoda MM, Hwang SM, Pirtskhalava T, Decklever T, Curran GL, Ogrodnik M, Jurk D, Johnson KO et al (2017) Transplanted senescent cells induce an osteoarthritis-like condition in mice. J Gerontol A 72:780–785CrossRefGoogle Scholar
  235. Xu M, Pirtskhalava T, Farr JN, Weigand BM, Palmer AK, Weivoda MM, Inman CL, Ogrodnik MB, Hachfeld CM, Fraser DG et al (2018) Senolytics improve physical function and increase lifespan in old age. Nat Med 24:1246CrossRefPubMedPubMedCentralGoogle Scholar
  236. Xue J, Rai V, Singer D, Chabierski S, Xie J, Reverdatto S, Burz DS, Schmidt AM, Hoffmann R, Shekhtman A (2011) Advanced glycation end product recognition by the receptor for AGEs. Struct Lond Engl 1993(19):722–732Google Scholar
  237. Xue J, Ray R, Singer D, Böhme D, Burz DS, Rai V, Hoffmann R, Shekhtman A (2014) The receptor for advanced glycation end products (RAGE) specifically recognizes methylglyoxal-derived AGEs. Biochemistry 53:3327–3335CrossRefPubMedPubMedCentralGoogle Scholar
  238. Yamagishi S, Matsui T, Fukami K (2015) Role of receptor for advanced glycation end products (RAGE) and its ligands in cancer risk. Rejuvenation Res 18:48–56CrossRefPubMedGoogle Scholar
  239. Yamamoto H, Watanabe T, Yamamoto Y, Yonekura H, Munesue S, Harashima A, Ooe K, Hossain S, Saito H, Murakami N (2007) RAGE in diabetic nephropathy. Curr Mol Med 7:752–757CrossRefPubMedGoogle Scholar
  240. Yamamoto Y, Harashima A, Saito H, Tsuneyama K, Munesue S, Motoyoshi S, Han D, Watanabe T, Asano M, Takasawa S et al (2011) Septic shock is associated with receptor for advanced glycation end products ligation of LPS. J Immunol Baltim Md 1950(186):3248–3257Google Scholar
  241. Yan SD, Chen X, Fu J, Chen M, Zhu H, Roher A, Slattery T, Zhao L, Nagashima M, Morser J et al (1996) RAGE and amyloid-beta peptide neurotoxicity in Alzheimer’s disease. Nature 382:685–691CrossRefPubMedGoogle Scholar
  242. Yan SD, Zhu H, Zhu A, Golabek A, Du H, Roher A, Yu J, Soto C, Schmidt AM, Stern D et al (2000) Receptor-dependent cell stress and amyloid accumulation in systemic amyloidosis. Nat Med 6:643–651CrossRefPubMedGoogle Scholar
  243. Yan SD, Bierhaus A, Nawroth PP, Stern DM (2009a) RAGE and Alzheimer’s disease: a progression factor for amyloid-β-induced cellular perturbation? J Alzheimers Dis JAD 16:833–843CrossRefPubMedGoogle Scholar
  244. Yan SF, Yan SD, Ramasamy R, Schmidt AM (2009b) Tempering the wrath of RAGE: an emerging therapeutic strategy against diabetic complications, neurodegeneration, and inflammation. Ann Med 41:408–422CrossRefPubMedPubMedCentralGoogle Scholar
  245. Yang HY, Chuang SY, Fang WH, Huang GS, Wang CC, Huang YY, Chu MY, Lin C, Su W, Chen CY et al (2015) Effect of RAGE polymorphisms on susceptibility to and severity of osteoarthritis in a Han Chinese population: a case-control study. Genet Mol Res GMR 14:11362–11370CrossRefPubMedGoogle Scholar
  246. Yao X, Carlson D, Sun Y, Ma L, Wolf SE, Minei JP, Zang QS (2015) Mitochondrial ROS induces cardiac inflammation via a pathway through mtDNA damage in a pneumonia-related sepsis model. PLoS ONE 10:e0139416CrossRefPubMedPubMedCentralGoogle Scholar
  247. Yatime L, Andersen GR (2013) Structural insights into the oligomerization mode of the human receptor for advanced glycation end-products. FEBS J 280:6556–6568CrossRefPubMedGoogle Scholar
  248. Yeh CH, Sturgis L, Haidacher J, Zhang XN, Sherwood SJ, Bjercke RJ, Juhasz O, Crow MT, Tilton RG, Denner L (2001) Requirement for p38 and p44/p42 mitogen-activated protein kinases in RAGE-mediated nuclear factor-kappaB transcriptional activation and cytokine secretion. Diabetes 50:1495–1504CrossRefPubMedGoogle Scholar
  249. Yu Y, Wang L, Delguste F, Durand A, Guilbaud A, Rousselin C, Schmidt AM, Tessier F, Boulanger E, Neviere R (2017) Advanced glycation end products receptor RAGE controls myocardial dysfunction and oxidative stress in high-fat fed mice by sustaining mitochondrial dynamics and autophagy-lysosome pathway. Free Radic Biol Med 112:397–410CrossRefPubMedGoogle Scholar
  250. Yu W, Tao M, Zhao Y, Hu X, Wang M (2018) 4′-Methoxyresveratrol alleviated AGE-induced inflammation via RAGE-mediated NF-κB and NLRP3 inflammasome pathway. Mol J Synth Chem Nat Prod, Chem, p 23Google Scholar
  251. Zeng S, Zhang QY, Huang J, Vedantham S, Rosario R, Ananthakrishnan R, Yan SF, Ramasamy R, DeMatteo RP, Emond JC et al (2012) Opposing roles of RAGE and Myd88 signaling in extensive liver resection. FASEB J 26:882–893CrossRefPubMedPubMedCentralGoogle Scholar
  252. Zhang L, Bukulin M, Kojro E, Roth A, Metz VV, Fahrenholz F, Nawroth PP, Bierhaus A, Postina R (2008) Receptor for advanced glycation end products is subjected to protein ectodomain shedding by metalloproteinases. J Biol Chem 283:35507–35516CrossRefPubMedGoogle Scholar
  253. Zhang H, Puleston DJ, Simon AK (2016) Autophagy and Immune Senescence. Trends Mol Med 22:671–686CrossRefPubMedGoogle Scholar
  254. Zong H, Madden A, Ward M, Mooney MH, Elliott CT, Stitt AW (2010) Homodimerization is essential for the receptor for advanced glycation end products (RAGE)-mediated signal transduction. J Biol Chem 285:23137–23146CrossRefPubMedPubMedCentralGoogle Scholar
  255. Zwielehner J, Liszt K, Handschur M, Lassl C, Lapin A, Haslberger AG (2009) Combined PCR-DGGE fingerprinting and quantitative-PCR indicates shifts in fecal population sizes and diversity of Bacteroides, bifidobacteria and Clostridium cluster IV in institutionalized elderly. Exp Gerontol 44:440–446CrossRefPubMedGoogle Scholar

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© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Univ. Lille, Inserm, CHU Lille, U995 - LIRIC - Lille Inflammation Research International CenterLilleFrance
  2. 2.Department of Geriatrics and Ageing Biology, School of MedicineLille UniversityLilleFrance
  3. 3.Department of GeriatricsLille University HospitalLilleFrance

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