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Pharmacogenomic Analysis Indicates Potential of 1,5-isoquinolinediol as a Universal Anti-Aging Agent for Different Tissues

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, Jin Woo Choi

Oncotarget. 2015 Jul 10;6(19):17251-60.

PMID: 25980498

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP5154029-A	1,5-Isoquinolinediol		5154-02-9	Price

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