Hastings Janna, Mains Abraham, Virk Bhupinder, Rodriguez Nicolas, Murdoch Sharlene, Pearce Juliette, Bergmann Sven, Le Novère Nicolas, Casanueva Olivia
Department of Epigenetics, Babraham Institute, Cambridge, United Kingdom.
Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
Front Mol Biosci. 2019 Feb 6;6:2. doi: 10.3389/fmolb.2019.00002. eCollection 2019.
In this contribution, we describe a multi-omics systems biology study of the metabolic changes that occur during aging in . 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 and mathematical modeling, we predicted metabolic fluxes during early aging. We find that standard Flux Balance Analysis does not accurately predict 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 .
在本论文中，我们描述了一项关于[具体物种]衰老过程中发生的代谢变化的多组学系统生物学研究。我们从青年期到老年早期的多个时间点进行采样，研究涵盖了衰老的整个过程，包括转录组学和基于靶向质谱的代谢组学。为了聚焦于年龄导致的代谢变化，我们使用了两种代谢上接近野生型但条件性不育的菌株。将这些数据与[具体物种]代谢的全基因组模型以及数学建模相结合，我们预测了衰老早期的代谢通量。我们发现，标准的通量平衡分析不能准确预测实测通量，也无法预测与柠檬酸循环相关的年龄相关变化。我们提出了一种新的通量平衡分析方法，将生物量生成和靶向代谢组学信息相结合，以生成一个更适合衰老研究的目标函数。我们通过对柠檬酸循环中与年龄相关变化的详细案例研究验证了这种方法。我们的方法为研究[具体物种]正常衰老过程中的代谢变化提供了一个全面的、时间分辨的多组学和建模资源。
