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 via redox catalysts may reveal mechanisms of senescence and aging