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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.

journal_name

Prev Med

journal_title

Preventive medicine

authors

Rahman I,Kinnula VL,Gorbunova V,Yao H

doi

10.1016/j.ypmed.2011.11.014

subject

Has Abstract

pub_date

2012-05-01 00:00:00

pages

S20-8

eissn

0091-7435

issn

1096-0260

pii

S0091-7435(11)00477-4

journal_volume

54 Suppl

pub_type

杂志文章,评审

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