title: Anti-Inflamm-Aging Effects of Long-Term Caloric Restriction via Overexpression of SIGIRR to Inhibit NF-κB Signaling Pathway.
abstract: BACKGROUND
  Chronic inflammation is thought to be a determinant of the aging rate and longevity. Caloric restriction (CR) attenuates age-related increases in the systemic levels of several pro-inflammatory mediators, but the anti-inflammatory mechanisms of CR in the aging process remain unclear.
  
  
  METHODS
  Fisher 344 rats in a CR group were fed an amount of food corresponding to 60% of that fed to an ad libitum-fed (AL) group for 8 months. Biochemical analyses and renal pathological grading were used to analyze physiological status. Important signaling molecules in the Toll-like receptor/nuclear factor kappa-light-chain-enhancer of activated B cells (TLR/NF-κB) pathway were also analyzed by western blotting, immunofluorescence and immunohistochemistry.
  
  
  RESULTS
  1) Compared with AL feeding, CR decreased aging-mediated increases in both biochemical marker levels and renal pathological grading. 2) Single immunoglobulin IL-1 (IL-1)-related receptor (SIGIRR) expression decreased with increasing age, but CR led to overexpression. 3) The expression of TLR4 was significantly higher in the CR group than in the AL group. 4) SIGIRR overexpression decreased the expression of the adaptor molecules myeloid differentiation factor 88 (MyD88), IL-1 receptor-associated kinase 4 (IRAK4) and tumor necrosis factor receptor-associated factor 6 (TRAF6). 5) The levels of the inflammatory markers phospho-IκBα and phospho-NF-κB p65 decreased in the CR group.
  
  
  CONCLUSIONS
  The inflammatory response might be alleviated by SIGIRR via blockade of the TLR4/NF-κB signaling pathway. Therefore, CR can decrease inflammation via SIGIRR overexpression, and SIGIRR might be a new target to delay aging.
authors.forename: Xiao-meng
authors.initials: XM
authors.lastname: Xu
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Ning
authors.forename: Wen-juan
authors.initials: WJ
authors.lastname: Wang
authors.forename: Jie-qiong
authors.initials: JQ
authors.lastname: Liu
authors.forename: Xue-yuan
authors.initials: XY
authors.lastname: Bai
authors.forename: Xue-feng
authors.initials: XF
authors.lastname: Sun
authors.forename: Guang-yan
authors.initials: GY
authors.lastname: Cai
authors.forename: Xiang-mei
authors.initials: XM
authors.lastname: Chen
mesh_terms: D000375:Aging; D000818:Animals; D031204:Caloric Restriction; D007249:Inflammation; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D017472:Receptors, Interleukin-1; D048029:TNF Receptor-Associated Factor 6; D051197:Toll-Like Receptor 4; C000605977:IRAK4 protein, rat; D017346:Protein Serine-Threonine Kinases