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

Baumgart, Mario; Priebe, Steffen; Groth, Marco; Hartmann, Nils; Menzel, Uwe; Pandolfini, Luca; Koch, Philipp; Felder, Marius; Ristow, Michael; Englert, Christoph; Guthke, Reinhard; Platzer, Matthias; Cellerino, Alessandro

doi:10.1016/j.cels.2016.01.014

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.

Titolo:	Longitudinal RNA-Seq Analysis of Vertebrate Aging Identifies Mitochondrial Complex I as a Small-Molecule-Sensitive Modifier of Lifespan
Autori:	BAUMGART, Mario Priebe, Steffen Groth, Marco Hartmann, Nils Menzel, Uwe PANDOLFINI, LUCA Koch, Philipp Felder, Marius Ristow, Michael Englert, Christoph Guthke, Reinhard Platzer, Matthias CELLERINO, Alessandro mostra contributor esterni nascondi contributor esterni
Data di pubblicazione:	2016
Rivista:	CELL SYSTEMS
Digital Object Identifier (DOI):	http://dx.doi.org/10.1016/j.cels.2016.01.014
Settore Scientifico Disciplinare:	Settore BIO/09 - Fisiologia Settore BIO/18 - Genetica
Parole Chiave:	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
Handle:	http://hdl.handle.net/11384/64829
Appare nelle tipologie:	1.1 Articolo in rivista

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