Multi-Omics and Genome-Scale Modeling Reveal a Metabolic Shift During C. elegans Aging.

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Version: Final published version
Serval ID
serval:BIB_EE4830743295
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Multi-Omics and Genome-Scale Modeling Reveal a Metabolic Shift During C. elegans Aging.
Journal
Frontiers in Molecular Biosciences
Author(s)
Hastings J., Mains A., Virk B., Rodriguez N., Murdoch S., Pearce J., Bergmann S., Le Novère N., Casanueva O.
ISSN
2296-889X (Print)
ISSN-L
2296-889X
Publication state
Published
Issued date
2019
Peer-reviewed
Oui
Volume
6
Pages
2
Language
english
Abstract
In this contribution, we describe a multi-omics systems biology study of the metabolic changes that occur during aging in Caenorhabditis elegans. Sampling several time points from young adulthood until early old age, our study covers the full duration of aging and include transcriptomics, and targeted MS-based metabolomics. In order to focus on the metabolic changes due to age we used two strains that are metabolically close to wild-type, yet are conditionally non-reproductive. Using these data in combination with a whole-genome model of the metabolism of C. elegans and mathematical modeling, we predicted metabolic fluxes during early aging. We find that standard Flux Balance Analysis does not accurately predict in vivo measured fluxes nor age-related changes associated with the Citric Acid cycle. We present a novel Flux Balance Analysis method where we combined biomass production and targeted metabolomics information to generate an objective function that is more suitable for aging studies. We validated this approach with a detailed case study of the age-associated changes in the Citric Acid cycle. Our approach provides a comprehensive time-resolved multi-omics and modeling resource for studying the metabolic changes during normal aging in C. elegans.
Keywords
C. elegans, aging, flux balance analysis, metabolomics, multi-omics, systems biology, whole genome model
Pubmed
Web of science
Open Access
Yes
Create date
28/02/2019 8:23
Last modification date
20/08/2019 16:15
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