title: Longitudinal RNA-Seq Analysis of Vertebrate Aging Identifies Mitochondrial Complex I as a Small-Molecule-Sensitive Modifier of Lifespan.
abstract: Mutations and genetic variability affect gene expression and lifespan, but the impact of variations in gene expression within individuals on their aging-related mortality is poorly understood. We performed a longitudinal study in the short-lived killifish, Nothobranchius furzeri, and correlated quantitative variations in gene expression during early adult life with lifespan. Shorter- and longer-lived individuals differ in their gene expression before the onset of aging-related mortality; differences in gene expression are more pronounced early in life. We identified mitochondrial respiratory chain complex I as a hub in a module of genes whose expression is negatively correlated with lifespan. Accordingly, partial pharmacological inhibition of complex I by the small molecule rotenone reversed aging-related regulation of gene expression and extended lifespan in N. furzeri by 15%. These results support the use of N. furzeri as a vertebrate model for identifying the protein targets, pharmacological modulators, and individual-to-individual variability associated with aging.
authors.affiliation: Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Beutenbergstraße 11, 07745 Jena, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Baumgart
authors.affiliation: Leibniz Institute for Natural Product Research and Infection Biology-Hans Knöll Institute (HKI), Beutenbergstraße 11a, 07745 Jena, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Priebe
authors.affiliation: Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Beutenbergstraße 11, 07745 Jena, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Groth
authors.affiliation: Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Beutenbergstraße 11, 07745 Jena, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Hartmann
authors.affiliation: Leibniz Institute for Natural Product Research and Infection Biology-Hans Knöll Institute (HKI), Beutenbergstraße 11a, 07745 Jena, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Menzel
authors.affiliation: Scuola Normale Superiore, Laboratory of Biology, c/o Istituto di Biofisica del CNR, via Moruzzi 1, 56124 Pisa, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Pandolfini
authors.affiliation: Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Beutenbergstraße 11, 07745 Jena, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Koch
authors.affiliation: Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Beutenbergstraße 11, 07745 Jena, Germany.
authors.forename: Marius
authors.initials: M
authors.lastname: Felder
authors.affiliation: Energy Metabolism Laboratory, ETH Zürich (Swiss Federal Institute of Technology), Schorenstrasse 16, 8603 Schwerzenbach-Zürich, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Ristow
authors.affiliation: Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Beutenbergstraße 11, 07745 Jena, Germany; Faculty of Biology and Pharmacy, Friedrich Schiller University Jena, 07743 Jena, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Englert
authors.affiliation: Leibniz Institute for Natural Product Research and Infection Biology-Hans Knöll Institute (HKI), Beutenbergstraße 11a, 07745 Jena, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Guthke
authors.affiliation: Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Beutenbergstraße 11, 07745 Jena, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Platzer
authors.affiliation: Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Beutenbergstraße 11, 07745 Jena, Germany; Scuola Normale Superiore, Laboratory of Biology, c/o Istituto di Biofisica del CNR, via Moruzzi 1, 56124 Pisa, Italy. Electronic address: alessandro.cellerino@sns.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cellerino
mesh_terms: D000818:Animals; D003532:Cyprinodontiformes; D008137:Longitudinal Studies; D012313:RNA; D017423:Sequence Analysis, RNA; D014714:Vertebrates
chemical_list: D012313:RNA
keywords: GAGE; Nothobranchius furzeri; RNA transport; RNA-seq; aging; history trait; hormesis; hourglass; life ribosome; lifespan regulation; longevity; longitudinal study; mitohormesis; rejuvenation; weighted gene coexpression network analysis (WGCNA); zebrafish