Hindawi Publishing Corporation Oxidative Medicine and Cellular Longevity Volume 2012, Article ID 850684, 13 pages doi:10.1155/2012/850684 Research Article Preventive Effects of Epigallocatechin-3-O -Gallate against Replicative Senescence Associated with p53 Acetylation in Human Dermal Fibroblasts Dong-Wook Han, 1 Mi Hee Lee, 2 Bongju Kim, 3 Jun Jae Lee, 1, 4 Suong-Hyu Hyon, 4 and Jong-Chul Park 2 1 Department of Applied Nanoscience and BK 21 Nano Fusion Technology Division, College of Nanoscience & Nanotechnology, Pusan National University, San 30 Jangjeon-dong, Geumjeong-gu, Busan 609-735, Republic of Korea 2 Cellbiocontrol Laboratory, Department of Medical Engineering, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, Republic of Korea 3 Center for Innovation in Immunoregulative Technology and Therapeutics, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan 4 Department of Biobased Materials Science, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan Correspondence should be addressed to Dong-Wook Han, nanohan@pusan.ac.kr and Jong-Chul Park, parkjc@yuhs.ac Received 19 July 2012; Revised 17 September 2012; Accepted 8 October 2012 Academic Editor: Gabriele Saretzki Copyright © 2012 Dong-Wook Han 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. Considering the various pharmacological activities of epigallocatechin-3-O-gallate (EGCG) including anticancer, and anti- inflammatory, antidiabetic, and so forth, relatively less attention has been paid to the antiaging effect of EGCG on primary cells. In this study, the preventive effects of EGCG against serial passage-induced senescence were investigated in primary cells including rat vascular smooth muscle cells (RVSMCs), human dermal fibroblasts (HDFs), and human articular chondrocytes (HACs). The involvement of Sirt1 and acetylated p53 was examined as an underlying mechanism for the senescence preventive activity of EGCG in HDFs. All cells were employed with the initial passage number (PN) between 3 and 7. For inducing senescence, the cells were serially passaged at the predetermined times and intervals in the absence or presence of EGCG (50 or 100 μM). Serial passage- induced senescence in RVSMCs and HACs was able to be significantly prevented at 50 μM EGCG, while in HDFs, 100 μM EGCG could significantly prevent senescence and recover their cell cycle progression close to the normal level. Furthermore, EGCG was found to prevent serial passage- and H 2 O 2 -induced senescence in HDFs by suppressing p53 acetylation, but the Sirt1 activity was unaffected. In addition, proliferating HDFs showed similar cellular uptake of FITC-conjugated EGCG into the cytoplasm with their senescent counterparts but different nuclear translocation of it from them, which would partly account for the differential responses to EGCG in proliferating versus senescent cells. Taking these results into consideration, it is suggested that EGCG may be exploited to craft strategies for the development of an antiaging or age-delaying agent. 1. Introduction Cellular senescence means a state of irreversible growth arrest by which normal cells lose the ability to divide generally after about 50 cell divisions in vitro [1]. Some cells become senescent after fewer replication cycles as a result of DNA double-strand breaks. This phenomenon, also known as replicative senescence, was first reported by Hayflick and Moorhead observing that normal human fibroblasts were able to enter a state of irreversible growth arrest after serial cultivation in vitro; meanwhile cancer cells did not enter this growth arrest state and proliferated indefinitely [1]. Cellular senescence can be triggered by multiple mechanisms including telomere shortening, the epigenetic derepression of the cyclin-dependent kinase (CDK) inhibitor 2A locus, and DNA damage [2]. Moreover, these mechanisms limit