title: Pharmacogenomic analysis indicates potential of 1,5-isoquinolinediol as a universal anti-aging agent for different tissues.
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.
authors.affiliation: Institute for Metabolic Disease, School of Medicine, Wonkwang University, Iksan, Jeonbuk, South Korea.
authors.forename: Mi Sung
authors.initials: MS
authors.lastname: Park
authors.affiliation: College of Pharmacy, Catholic University of Daegu, Gyeongbuk, South Korea.
authors.forename: Joon-Seok
authors.initials: JS
authors.lastname: Choi
authors.affiliation: Department of Oral and Maxillofacial Radiology, College of Dentistry, Wonkwang University, Jeonbuk, South Korea.
authors.forename: Wan
authors.initials: W
authors.lastname: Lee
authors.affiliation: Wonkwang Institute of Integrative Biomedical Science and Dental Research Institute, School of Dentistry, Wonkwang University, Iksan, Chonbuk, South Korea.
authors.forename: Yoon Jung
authors.initials: YJ
authors.lastname: Yang
authors.affiliation: Wonkwang Institute of Integrative Biomedical Science and Dental Research Institute, School of Dentistry, Wonkwang University, Iksan, Chonbuk, South Korea.
authors.forename: Juhee
authors.initials: J
authors.lastname: Kim
authors.affiliation: Wonkwang Institute of Integrative Biomedical Science and Dental Research Institute, School of Dentistry, Wonkwang University, Iksan, Chonbuk, South Korea.
authors.forename: Gun-Joo
authors.initials: GJ
authors.lastname: Lee
authors.affiliation: Jaesaeng Hospital, Biomedical Research Institute, Seongnam, Gyenggi-do, South Korea.
authors.forename: Sang Soo
authors.initials: SS
authors.lastname: Kim
authors.affiliation: Institute for Metabolic Disease, School of Medicine, Wonkwang University, Iksan, Jeonbuk, South Korea.|Division of Cardiothoracic Radiology, Department of Radiology, School Of Medicine, Wonkwang University, Iksan, Jeonbuk, South Korea.
authors.forename: Seong Hoon
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Acupuncture and Moxibustion, Wonkwang University Oriental Medical Hospital, Gwangju, South Korea.
authors.forename: Sung Chul
authors.initials: SC
authors.lastname: Kim
authors.affiliation: Wonkwang Institute of Integrative Biomedical Science and Dental Research Institute, School of Dentistry, Wonkwang University, Iksan, Chonbuk, South Korea.|Advanced Institute of Convergence Technology, Seoul National University, Suwon, Gyenggi-do, South Korea.
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Choi
mesh_terms: D000375:Aging / Q000187:drug effects*; D000818:Animals; D015153:Blotting, Western; D016922:Cellular Senescence / Q000187:drug effects*; D020869:Gene Expression Profiling; D007546:Isoquinolines / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D010597:Pharmacogenetics; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000494:pharmacology*
chemical_list: D007546:Isoquinolines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C095653:1,5-dihydroxyisoquinoline
keywords: aging; cellular replicative senescence; chemical genomics; gene expression profile