期刊
FRONTIERS IN MOLECULAR BIOSCIENCES
卷 6, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fmolb.2019.00002
关键词
metabolomics; flux balance analysis; aging; systems biology; multi-omics; whole genome model; C. elegans
资金
- ERC [638426]
- BBSRC [BBS/E/B000C0426]
- MRC [MR/J003808/1]
- Rutherford Foundation Fellowship
- NIH [1S10OD021562-01]
- BBSRC [BBS/E/B/000C0434, BBS/E/B/000C0433, BBS/E/B/000C0423, BBS/E/B/000C0426, BBS/E/B/000C0425, BBS/E/B/000C0432] Funding Source: UKRI
- European Research Council (ERC) [638426] Funding Source: European Research Council (ERC)
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据