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Oxidative Medicine and Cellular Longevity
Volume 2013, Article ID 680414, 10 pages
http://dx.doi.org/10.1155/2013/680414
Research Article

Accelerated Aging during Chronic Oxidative Stress: A Role for PARP-1

Department of Toxicology, Maastricht University, P.O. Box 6200 MD, Maastricht, The Netherlands

Received 1 August 2013; Revised 20 September 2013; Accepted 23 September 2013

Academic Editor: David Vauzour

Copyright © 2013 Daniëlle M. P. H. J. Boesten et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Oxidative stress plays a major role in the pathophysiology of chronic inflammatory disease and it has also been linked to accelerated telomere shortening. Telomeres are specialized structures at the ends of linear chromosomes that protect these ends from degradation and fusion. Telomeres shorten with each cell division eventually leading to cellular senescence. Research has shown that poly(ADP-ribose) polymerase-1 (PARP-1) and subtelomeric methylation play a role in telomere stability. We hypothesized that PARP-1 plays a role in accelerated aging in chronic inflammatory diseases due to its role as coactivator of NF-κb and AP-1. Therefore we evaluated the effect of chronic PARP-1 inhibition (by fisetin and minocycline) in human fibroblasts (HF) cultured under normal conditions and under conditions of chronic oxidative stress, induced by tert-butyl hydroperoxide (t-BHP). Results showed that PARP-1 inhibition under normal culturing conditions accelerated the rate of telomere shortening. However, under conditions of chronic oxidative stress, PARP-1 inhibition did not show accelerated telomere shortening. We also observed a strong correlation between telomere length and subtelomeric methylation status of HF cells. We conclude that chronic PARP-1 inhibition appears to be beneficial in conditions of chronic oxidative stress but may be detrimental under relatively normal conditions.