title: SIRT1 as a therapeutic target in inflammaging of the pulmonary disease.
abstract: OBJECTIVE
  Chronic inflammation and cellular senescence are intertwined in the pathogenesis of premature aging, which is considered as an important contributing factor in driving chronic obstructive pulmonary disease (COPD). Sirtuin1 (SIRT1), a nicotinamide adenine dinucleotide (NAD(+))-dependent protein/histone deacetylase, regulates inflammation, senescence/aging, stress resistance, and deoxyribonucleic acid (DNA) damage repair via deacetylating intracellular signaling molecules and chromatin histones. The present review describes the mechanism and regulation of SIRT1 by environmental agents/oxidants/reactive aldehydes and pro-inflammatory stimuli in lung inflammation and aging. The role of dietary polyphenols in regulation of SIRT1 in inflammaging is also discussed.
  
  
  METHODS
  Analysis of current research findings on the mechanism of inflammation and senescence/aging (i.e., inflammaging) and their regulation by SIRT1 in premature aging of the lung.
  
  
  RESULTS
  COPD is a disease of the lung inflammaging, which is associated with the DNA damage response, transcription activation and chromatin modifications. SIRT1 regulates inflammaging via regulating forkhead box class O 3, p53, nuclear factor kappa B, histones and various proteins involved in DNA damage and repair. Polyphenols and its analogs have been shown to activate SIRT1 although they have anti-inflammatory and antioxidant properties.
  
  
  CONCLUSIONS
  Targeting lung inflammation and cellular senescence as well as premature lung aging using pharmacological SIRT1 activators or polyphenols would be a promising therapeutic intervention for COPD/emphysema.
authors.affiliation: Department of Environmental Medicine, Lung Biology and Disease Program, University of Rochester Medical Center, Rochester, NY 14642, USA. irfan_rahman@urmc.rochester.edu
authors.forename: Irfan
authors.initials: I
authors.lastname: Rahman
authors.forename: Vuokko L
authors.initials: VL
authors.lastname: Kinnula
authors.forename: Vera
authors.initials: V
authors.lastname: Gorbunova
authors.forename: Hongwei
authors.initials: H
authors.lastname: Yao
mesh_terms: D019588:Aging, Premature / Q000378:metabolism; D016922:Cellular Senescence / Q000502:physiology; D004249:DNA Damage; D006801:Humans; D018384:Oxidative Stress; D059808:Polyphenols / Q000494:pharmacology; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D011656:Pulmonary Emphysema / Q000188:drug therapy; D056564:Sirtuin 1 / Q000187:drug effects* / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D059808:Polyphenols; D056564:Sirtuin 1