| Project/Area Number |
18K18451
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Studies on the Super-Aging Society
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
横出 正之 京都大学, 医学研究科, 教授 (20252447)
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| Project Period (FY) |
2018-06-29 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
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| Keywords | 老化 / メタボライト |
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| Outline of Final Research Achievements |
During human fasting, metabolic markers, including butyrates, carnitines, and branched-chain amino acids, are upregulated for energy substitution. We performed non-targeted, accurate semiquantitative metabolomic analysis of human whole blood, plasma, and red blood cells during 34-58 hr fasting of four volunteers. During this period, 44 of 130 metabolites increased 1.5 to 60-fold. Consistently fourteen were previously reported. Metabolites in pentose phosphate pathway are abundant, probably due to demand for antioxidants, NADPH, gluconeogenesis and anabolic metabolism. Global increases of TCA cycle-related compounds reflect enhanced mitochondrial activity in tissues during fasting. Enhanced purine/pyrimidine metabolites support RNA/protein synthesis and transcriptional reprogramming. Thus diverse, pronounced metabolite increases result from greatly activated catabolism and anabolism stimulated by fasting. Anti-oxidation may be a principal response to fasting.
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| Academic Significance and Societal Importance of the Research Achievements |
基礎老化研究で長年カロリー制限仮説が注目されてきたことに鑑み、ヒト飢餓メタボローム解析を行い、44個のメタボライト上昇という意外な成果を得た。発表論文は、2019年の約2万本のScietific Reportsジャーナル論文の中で、ダウンロード数のトップ100にランクインした。本成果は、飢餓による健康効果の臨床応用の基盤となる。
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