Oncotarget

Research Papers:

Pharmacogenomic analysis indicates potential of 1,5-isoquinolinediol as a universal anti-aging agent for different tissues

Mi Sung Park, Joon-Seok Choi, Wan Lee, Yoon Jung Yang, Juhee Kim, Gun-Joo Lee, Sang Soo Kim, Seong Hoon Park, Sung Chul Kim and Jin Woo Choi _

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Oncotarget. 2015; 6:17251-17260. https://doi.org/10.18632/oncotarget.3949

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Abstract

Mi Sung Park1,*, Joon-Seok Choi2,*, Wan Lee3,*, Yoon Jung Yang4, Juhee Kim4, Gun-Joo Lee4, Sang Soo Kim5, Seong Hoon Park1,6, Sung Chul Kim7 and Jin Woo Choi4,8

1 Institute for Metabolic Disease, School of Medicine, Wonkwang University, Iksan, Jeonbuk, South Korea

2 College of Pharmacy, Catholic University of Daegu, Gyeongbuk, South Korea

3 Department of Oral and Maxillofacial Radiology, College of Dentistry, Wonkwang University, Jeonbuk, South Korea

4 Wonkwang Institute of Integrative Biomedical Science and Dental Research Institute, School of Dentistry, Wonkwang University, Iksan, Chonbuk, South Korea

5 Jaesaeng Hospital, Biomedical Research Institute, Seongnam, Gyenggi-do, South Korea

6 Division of Cardiothoracic Radiology, Department of Radiology, School Of Medicine, Wonkwang University, Iksan, Jeonbuk, South Korea

7 Department of Acupuncture and Moxibustion, Wonkwang University Oriental Medical Hospital, Gwangju, South Korea

8 Advanced Institute of Convergence Technology, Seoul National University, Suwon, Gyenggi-do, South Korea

* These authors have contributed equally to this work

Correspondence to:

Jin Woo Choi, email:

Keywords: aging, cellular replicative senescence, gene expression profile, chemical genomics

Received: March 21, 2015 Accepted: April 08, 2015 Published: April 29, 2015

Abstract

The natural aging of multicellular organisms is marked by a progressive decline in the function of cells and tissues. The accumulation of senescent cells in tissues seems to eventually cause aging of the host. Nevertheless, gene expression that influences aging is unlikely to be conserved between tissues, and age-related loss of function seems to depend on a variety of mechanisms. This is a concern when developing anti-aging drugs in geriatric clinical pharmacology. We have sought a universal agent to redundantly cover gene expression despite the variation in differentially expressed genes between tissues. Using a minimally modified connectivity map, the poly (ADP-ribose) polymerase (PARP) inhibitor 1,5-isoquinolinediol was selected as a potent candidate, simultaneously applicable to various tissues. This choice was validated in vitro. Treatment of murine embryonic fibroblasts with 1,5-isoquinolinediol appeared to efficiently suppress the rate of replicative senescence at a concentration of 0.1 µM without resulting in cell death. The appearance of abnormal nuclei and accumulation of β-galactosidase in the cytoplasm were inhibited by daily treatment with the agent. When the aging process was accelerated by hydroxyurea-induced oxidative stress, the effect was even more noticeable. Thus, 1,5-isoquinolinediol may potentially be developed as an agent to prolong life.


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