RNA Seq report.tar.bz2

RNA-seq data for the following project: A high-throughput anti-aging drug screen was developed that simultaneously measures senescence-associated b-galactosidase activity and proliferation. Applied to replicatively pre-aged fibroblasts, this screen yielded violuric acid (VA) and 1-naphthoquinone-2-monoxime (N2N1) as its top two hits. These lead compounds extended the replicative life spans of normal and progeroid human cells in a dose-dependent manner and also extended the chronological life spans of mice and C. elegans. They are further shown here to function as redox catalysts in oxidations of NAD(P)H. They thus slow age-related declines in NAD(P)⁺/NAD(P)H ratios. VA participates in non-enzymatic electron transfers from NAD(P)H to oxidized glutathione or peroxides. N2N1 transfers electrons from NAD(P)H to cytochrome c or CoQ₁₀ via NAD(P)H dehydrogenase (quinone) 1 (NQO1). Our results indicate that pharmacologic manipulation of NQO1 activity <i>via</i> redox catalysts may reveal mechanisms of senescence and aging

本数据集对应如下研究项目的RNA测序（RNA-seq）数据：本研究开发了一种高通量抗衰老药物筛选模型，可同时检测衰老相关β-半乳糖苷酶（senescence-associated β-galactosidase）活性与细胞增殖状态。将该模型应用于复制性预衰老成纤维细胞后，筛选得到的Top2候选化合物为紫尿酸（violuric acid, VA）与1-萘醌-2-单肟（1-naphthoquinone-2-monoxime, N2N1）。这些先导化合物可呈剂量依赖性延长正常及早衰型人类细胞的复制寿命，同时可延长小鼠与秀丽隐杆线虫（C. elegans）的时序寿命。本研究进一步证实，二者可作为氧化还原催化剂参与还原型烟酰胺腺嘌呤二核苷酸（磷酸）（NAD(P)H）的氧化反应，因此可减缓衰老相关的NAD(P)⁺/NAD(P)H比值下降。其中，紫尿酸可介导NAD(P)H向氧化型谷胱甘肽或过氧化物的非酶促电子传递；1-萘醌-2-单肟则通过烟酰胺腺嘌呤二核苷酸磷酸还原酶（醌）1（NAD(P)H dehydrogenase (quinone) 1, NQO1）介导NAD(P)H向细胞色素c或辅酶Q₁₀（CoQ₁₀）的电子传递。本研究结果表明，通过氧化还原催化剂对NQO1活性进行药理学调控，或可揭示细胞衰老与机体衰老的潜在机制。