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Prev Med. 2012 May;54 Suppl:S20-8. doi: 10.1016/j.ypmed.2011.11.014. Epub 2011 Dec 8.

SIRT1 as a therapeutic target in inflammaging of the pulmonary disease.

Author information

1
Department of Environmental Medicine, Lung Biology and Disease Program, University of Rochester Medical Center, Rochester, NY 14642, USA. irfan_rahman@urmc.rochester.edu

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.

KEYWORDS:

COPD; DNA damage response; FOXO3; Histone modifications; Inflammaging; NF-κB; Oxidative stress; Polyphenols; SIRT1; Tobacco smoke

PMID:
22178470
PMCID:
PMC3311735
DOI:
10.1016/j.ypmed.2011.11.014
[Indexed for MEDLINE]
Free PMC Article

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