PUBLICATION
Longitudinal RNA-Seq Analysis of Vertebrate Aging Identifies Mitochondrial Complex I as a Small-Molecule-Sensitive Modifier of Lifespan
- Authors
- Baumgart, M., Priebe, S., Groth, M., Hartmann, N., Menzel, U., Pandolfini, L., Koch, P., Felder, M., Ristow, M., Englert, C., Guthke, R., Platzer, M., Cellerino, A.
- ID
- ZDB-PUB-160503-2
- Date
- 2016
- Source
- Cell systems 2: 122-132 (Journal)
- Registered Authors
- Cellerino, Alessandro, Englert, Christoph
- 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
- Datasets
- GEO:GSE66362
- MeSH Terms
-
- Animals
- Cyprinodontiformes
- Longitudinal Studies
- RNA
- Sequence Analysis, RNA
- Vertebrates*
- PubMed
- 27135165 Full text @ Cell Syst
Citation
Baumgart, M., Priebe, S., Groth, M., Hartmann, N., Menzel, U., Pandolfini, L., Koch, P., Felder, M., Ristow, M., Englert, C., Guthke, R., Platzer, M., Cellerino, A. (2016) Longitudinal RNA-Seq Analysis of Vertebrate Aging Identifies Mitochondrial Complex I as a Small-Molecule-Sensitive Modifier of Lifespan. Cell systems. 2:122-132.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping