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

Frontiers in Molecular Biosciences
Janna HastingsOlivia Casanueva

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 no...Continue Reading

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Citations

Sep 23, 2020·Nature Reviews. Microbiology·Xin FangBernhard O Palsson
Oct 27, 2020·Frontiers in Aging Neuroscience·Nicholas S KronLynne A Fieber
Nov 17, 2020·Frontiers in Molecular Biosciences·Timothy E HoffmanJulie A Moreno
Jan 21, 2021·Metabolites·Jiaming Xu, Stefan Taubert
Mar 4, 2021·Aging Cell·David H Meyer, Björn Schumacher
Mar 4, 2021·Disease Models & Mechanisms·Marte MolenaarsRiekelt H Houtkooper
Jun 11, 2021·Nature Communications·Andrea AnnibalAdam Antebi
Jun 29, 2021·Frontiers in Genetics·Serena DatoFrancesco Lescai
Aug 3, 2021·Journal of Molecular Biology·Krishan GuptaDebarka Sengupta
Dec 22, 2020·Trends in Biotechnology·Yonghao CuiKang Zhou
Aug 24, 2021·Disease Models & Mechanisms·Marte MolenaarsRiekelt H Houtkooper
Aug 31, 2021·Journal of the American Chemical Society·Chester J J WrobelFrank C Schroeder

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Datasets Mentioned

BETA
GSE124994

Methods Mentioned

BETA
PCR
Chip
metabolomics assay
protein folding

Software Mentioned

R package “ ropls ”
R library
Multiquant
PLS
prcomp
FEM
Metab
CobraPy
Pathview
Sciex Analyst

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