Longitudinal RNA-Seq Analysis of Vertebrate Aging Identifies Mitochondrial Complex I as a Small-Molecule-Sensitive Modifier of LifespanReportar como inadecuado


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


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Publication Date: 2016-02-24

Journal Title: Cell Systems

Publisher: Elsevier

Volume: 2

Issue: 2

Pages: 122-132

Language: English

Type: Article

Metadata: Show full item record

Citation: Baumgart, M., Priebe, S., Groth, M., Hartmann, N., Menzel, U., Pandolfini, L., Koch, P., et al. (2016). Longitudinal RNA-Seq Analysis of Vertebrate Aging Identifies Mitochondrial Complex I as a Small-Molecule-Sensitive Modifier of Lifespan. Cell Systems, 2 (2), 122-132.

Description: This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.cels.2016.01.014

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.

Keywords: aging, GAGE, history trait, hormesis, hourglass, life ribosome, lifespan regulation, longevity, longitudinal study, mitohormesis, Nothobranchius furzeri, rejuvenation, RNA transport, RNA-seq, weighted gene coexpression network analysis (WGCNA), zebrafish

Sponsorship: We thank Sabine Matz, Christin Hahn, Ivonne Heinze, and Ivonne Goerlich for technical assistance and Giorgio Bianchini for drawing. This work was partially supported by the German Ministry for Education and Research (JenAge; BMBF, support codes: 0315581A and 0315581C) and by intramural grant of Scuola Normale Superiore.

Identifiers:

This record's URL: http://dx.doi.org/10.1016/j.cels.2016.01.014https://www.repository.cam.ac.uk/handle/1810/254080

Rights: Attribution-NonCommercial-NoDerivs 2.0 UK: England & Wales

Licence URL: http://creativecommons.org/licenses/by-nc-nd/2.0/uk/





Autor: Baumgart, MarioPriebe, SteffenGroth, MarcoHartmann, NilsMenzel, UwePandolfini, LucaKoch, PhilippFelder, MariusRistow, MichaelEngle

Fuente: https://www.repository.cam.ac.uk/handle/1810/254080



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