Global stable-isotope tracing metabolomics reveals system-wide metabolic alternations in aging Drosophila

Ruohong Wang, Yandong Yin, Jingshu Li, Hongmiao Wang, Wanting Lv, Yang Gao, Tangci Wang, Yedan Zhong, Zhiwei Zhou, Yuping Cai, Xiaoyang Su, Nan Liu, Zheng Jiang Zhu

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

System-wide metabolic homeostasis is crucial for maintaining physiological functions of living organisms. Stable-isotope tracing metabolomics allows to unravel metabolic activity quantitatively by measuring the isotopically labeled metabolites, but has been largely restricted by coverage. Delineating system-wide metabolic homeostasis at the whole-organism level remains challenging. Here, we develop a global isotope tracing metabolomics technology to measure labeled metabolites with a metabolome-wide coverage. Using Drosophila as an aging model organism, we probe the in vivo tracing kinetics with quantitative information on labeling patterns, extents and rates on a metabolome-wide scale. We curate a system-wide metabolic network to characterize metabolic homeostasis and disclose a system-wide loss of metabolic coordinations that impacts both intra- and inter-tissue metabolic homeostasis significantly during Drosophila aging. Importantly, we reveal an unappreciated metabolic diversion from glycolysis to serine metabolism and purine metabolism as Drosophila aging. The developed technology facilitates a system-level understanding of metabolic regulation in living organisms.

Original languageEnglish (US)
Article number3518
JournalNature communications
Volume13
Issue number1
DOIs
StatePublished - Dec 2022

All Science Journal Classification (ASJC) codes

  • General Physics and Astronomy
  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology

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