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Longitudinal RNA-Seq Analysis of Vertebrate Aging Identifies Mitochondrial Complex I as a Small-Molecule-Sensitive Modifier of Lifespan.

  • Baumgart M Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Beutenbergstraße 11, 07745 Jena, Germany.
  • Priebe S Leibniz Institute for Natural Product Research and Infection Biology-Hans Knöll Institute (HKI), Beutenbergstraße 11a, 07745 Jena, Germany.
  • Groth M Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Beutenbergstraße 11, 07745 Jena, Germany.
  • Hartmann N Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Beutenbergstraße 11, 07745 Jena, Germany.
  • Menzel U Leibniz Institute for Natural Product Research and Infection Biology-Hans Knöll Institute (HKI), Beutenbergstraße 11a, 07745 Jena, Germany.
  • Pandolfini L Scuola Normale Superiore, Laboratory of Biology, c/o Istituto di Biofisica del CNR, via Moruzzi 1, 56124 Pisa, Italy.
  • Koch P Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Beutenbergstraße 11, 07745 Jena, Germany.
  • Felder M Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Beutenbergstraße 11, 07745 Jena, Germany.
  • Ristow M Energy Metabolism Laboratory, ETH Zürich (Swiss Federal Institute of Technology), Schorenstrasse 16, 8603 Schwerzenbach-Zürich, Switzerland.
  • Englert C 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.
  • Guthke R Leibniz Institute for Natural Product Research and Infection Biology-Hans Knöll Institute (HKI), Beutenbergstraße 11a, 07745 Jena, Germany.
  • Platzer M Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Beutenbergstraße 11, 07745 Jena, Germany.
  • Cellerino A 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.
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  • 2016-05-03
Published in:
  • Cell systems. - 2016
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
Animals
Cyprinodontiformes
Longitudinal Studies
RNA
Sequence Analysis, RNA
Vertebrates
English 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.
Language
  • English
Open access status
hybrid
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Persistent URL
https://sonar.ch/global/documents/253973
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