Metabolomic signature associated with reproduction-regulated aging inCaenorhabditis elegans.
InCaenorhabditis elegans (C. elegans), ablation of germline stem cells (GSCs) leads to infertility, which extends lifespan. It has been reported that aging and reproduction are both inextricably associated with metabolism. However, few studies have investigated the roles of polar small molecules metabolism in regulating longevity by reproduction. In this work, we combined the nuclear magnetic resonance (NMR) and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) to profile the water-soluble metabolome inC. elegans. Comparing the metabolic fingerprint between two physiological ages among different mutants, our results demonstrate that aging is characterized by metabolome remodeling and metabolic decline. In addition, by analyzing the metabolic profiles of long-lived germline-lessglp-1mutants, we discovered thatglp-1mutants regulate the levels of many age-variant metabolites to attenuate aging, including elevated concentrations of the pyrimidine and purine metabolism intermediates and decreased concentrations of the citric acid cycle intermediates. Interestingly, by analyzing the metabolome ofdaf-16;glp-1double mutants, our results revealed that some metabolic exchange contributing to germline-mediated longevity was mediated by transcription factor FOXO/DAF-16, including pyrimidine metabolism and the TCA cycle. Based on a comprehensive metabolic analysis, we provide novel insight into the relationship between longevity and metabolism regulated by germline signals inC. elegans.
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, Yunnan 650201, China.|University of Chinese Academy of Sciences, Beijing 100039, China.|Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming, Yunnan 650201, China.
Qin-Li
QL
Wan
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, Yunnan 650201, China.|Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming, Yunnan 650201, China.
Xiaohuo
X
Shi
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, Yunnan 650201, China.|Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming, Yunnan 650201, China.
Jiangxin
J
Liu
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, Yunnan 650201, China.|University of Chinese Academy of Sciences, Beijing 100039, China.|Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming, Yunnan 650201, China.
Ai-Jun
AJ
Ding
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, Yunnan 650201, China.|University of Chinese Academy of Sciences, Beijing 100039, China.|Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming, Yunnan 650201, China.
Yuan-Zhu
YZ
Pu
Shineway Pharmaceutical Co., Ltd, Sanhe, Hebei 065201, China.
Zhigang
Z
Li
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, Yunnan 650201, China.|Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming, Yunnan 650201, China.|Key Laboratory for Aging and Regenerative Medicine, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China.
Gui-Sheng
GS
Wu
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, Yunnan 650201, China.|Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming, Yunnan 650201, China.|Key Laboratory for Aging and Regenerative Medicine, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China.
Huai-Rong
HR
Luo
D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D008136:Longevity / Q000502:physiology*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D055432:Metabolomics; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; C060620:Glp-1 protein, C elegans; D051880:Receptors, Notch
Caenorhabditis elegans; UPLC-MS and NMR; aging; metabolome; reproduction