Dietary citrate supplementation enhances longevity, metabolic health, and memory performance through promoting ketogenesis

被引：33
作者：
Fan, Shou-Zen [1 ]
Lin, Cheng-Sheng [2 ]
Wei, Yu-Wen [2 ]
Yeh, Sheng-Rong [1 ,2 ]
Tsai, Yi-Hsuan [2 ]
Lee, Andrew Chengyu [2 ]
Lin, Wei-Sheng [3 ]
Wang, Pei-Yu [2 ,4 ,5 ,6 ,7 ,8 ]
机构：
[1] Natl Taiwan Univ, Natl Taiwan Univ Hosp, Dept Anesthesiol, Taipei, Taiwan
[2] Natl Taiwan Univ, Coll Med, Grad Inst Brain & Mind Sci, Taipei, Taiwan
[3] Taipei Vet Gen Hosp, Dept Pediat, Taipei, Taiwan
[4] Natl Taiwan Univ, Neurobiol & Cognit Sci Ctr, Taipei, Taiwan
[5] Natl Taiwan Univ, PhD Program Translat Med, Taipei, Taiwan
[6] Acad Sinica, Taipei, Taiwan
[7] Natl Taiwan Univ, Taiwan Int Grad Program Interdisciplinary Neurosc, Taipei, Taiwan
[8] Taipei Med Univ, Coll Med Sci & Technol, Grad Inst Neural Regenerat Med, Taipei, Taiwan
来源：
AGING CELL | 2021年 / 20卷 / 12期
关键词：
dendritic spine; hippocampus; insulin; lifespan; EXTENDS LIFE-SPAN; CALORIC RESTRICTION; CAENORHABDITIS-ELEGANS; BETA-HYDROXYBUTYRATE; MAMMALIAN-INDY; FOOD-INTAKE; DROSOPHILA; MICE; DELETION; COA;
D O I：
10.1111/acel.13510
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
Citrate is an essential substrate for energy metabolism that plays critical roles in regulating cell growth and survival. However, the action of citrate in regulating metabolism, cognition, and aging at the organismal level remains poorly understood. Here, we report that dietary supplementation with citrate significantly reduces energy status and extends lifespan in Drosophila melanogaster. Our genetic studies in fruit flies implicate a molecular mechanism associated with AMP-activated protein kinase (AMPK), target of rapamycin (TOR), and ketogenesis. Mice fed a high-fat diet that supplemented with citrate or the ketone body beta-hydroxybutyrate (beta OHB) also display improved metabolic health and memory. These results suggest that dietary citrate supplementation may prove to be a useful intervention in the future treatment of age-related dysfunction.
引用
收藏
页数：15
相关论文
共 45 条
  • [1] Deletion of the Mammalian INDY Homo log Mimics Aspects of Dietary Restriction and Protects against Adiposity and Insulin Resistance in Mice
    Birkenfeld, Andreas L.
    Lee, Hui-Young
    Guebre-Egziabher, Fitsum
    Alves, Tiago C.
    Jurczak, Michael J.
    Jornayvaz, Francois R.
    Zhang, Dongyang
    Hsiao, Jennifer J.
    Martin-Montalvo, Alejandro
    Fischer-Rosinsky, Antje
    Spranger, Joachim
    Pfeiffer, Andreas F.
    Jordan, Jens
    Fromm, Martin F.
    Koenig, Joerg
    Lieske, Stefanie
    Carmean, Christopher M.
    Frederick, David W.
    Weismann, Dirk
    Knauf, Felix
    Irusta, Pablo M.
    De Cabo, Rafael
    Helfand, Stephen L.
    Samuel, Varman T.
    Shulman, Gerald I.
    [J]. CELL METABOLISM, 2011, 14 (02) : 184 - 195
  • [2] PURIFICATION AND CHARACTERIZATION OF THE AMP-ACTIVATED PROTEIN-KINASE - COPURIFICATION OF ACETYL-COA CARBOXYLASE KINASE AND 3-HYDROXY-3-METHYLGLUTARYL-COA REDUCTASE KINASE-ACTIVITIES
    CARLING, D
    CLARKE, PR
    ZAMMIT, VA
    HARDIE, DG
    [J]. EUROPEAN JOURNAL OF BIOCHEMISTRY, 1989, 186 (1-2): : 129 - 136
  • [3] Molecular and functional analysis of SDCT2, a novel rat sodium-dependent dicarboxylate transporter
    Chen, XM
    Tsukaguchi, H
    Chen, XZ
    Berger, UV
    Hediger, MA
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1999, 103 (08) : 1159 - 1168
  • [4] The metabolite α-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR
    Chin, Randall M.
    Fu, Xudong
    Pai, Melody Y.
    Vergnes, Laurent
    Hwang, Heejun
    Deng, Gang
    Diep, Simon
    Lomenick, Brett
    Meli, Vijaykumar S.
    Monsalve, Gabriela C.
    Hu, Eileen
    Whelan, Stephen A.
    Wang, Jennifer X.
    Jung, Gwanghyun
    Solis, Gregory M.
    Fazlollahi, Farbod
    Kaweeteerawat, Chitrada
    Quach, Austin
    Nili, Mahta
    Krall, Abby S.
    Godwin, Hilary A.
    Chang, Helena R.
    Faull, Kym F.
    Guo, Feng
    Jiang, Meisheng
    Trauger, Sunia A.
    Saghatelian, Alan
    Braas, Daniel
    Christofk, Heather R.
    Clarke, Catherine F.
    Teitell, Michael A.
    Petrascheck, Michael
    Reue, Karen
    Jung, Michael E.
    Frand, Alison R.
    Huang, Jing
    [J]. NATURE, 2014, 510 (7505) : 397 - 401
  • [5] Dommerholt MB, 2018, J ENDOCRINOL, V237, P59, DOI [10.1530/JOE-17-0505, 10.1530/joe-17-0505]
  • [6] Mechanisms of amino acid-mediated lifespan extension in Caenorhabditis elegans
    Edwards, Clare
    Canfield, John
    Copes, Neil
    Brito, Andres
    Rehan, Muhammad
    Lipps, David
    Brunquell, Jessica
    Westerheide, Sandy D.
    Bradshaw, Patrick C.
    [J]. BMC GENETICS, 2015, 16
  • [7] D-beta-hydroxybutyrate extends lifespan in C. elegans
    Edwards, Clare
    Canfield, John
    Copes, Neil
    Rehan, Muhammad
    Lipps, David
    Bradshaw, Patrick C.
    [J]. AGING-US, 2014, 6 (08): : 621 - 644
  • [8] Nervous System Deletion of Mammalian INDY in Mice Mimics Dietary Restriction-Induced Memory Enhancement
    Fan, Shou-Zen
    Sung, Chih-Wei
    Tsai, Yi-Hsuan
    Yeh, Sheng-Rong
    Lin, Wei-Sheng
    Wang, Pei-Yu
    [J]. JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES, 2021, 76 (01): : 50 - 56
  • [9] Regulation of Ketone Body Metabolism and the Role of PPARα
    Grabacka, Maja
    Pierzchalska, Malgorzata
    Dean, Matthew
    Reiss, Krzysztof
    [J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2016, 17 (12):
  • [10] Tequila Regulates Insulin-Like Signaling and Extends Life Span in Drosophila melanogaster
    Huang, Cheng-Wen
    Wang, Horng-Dar
    Bai, Hua
    Wu, Ming-Shiang
    Yen, Jui-Hung
    Tatar, Marc
    Fu, Tsai-Feng
    Wang, Pei-Yu
    [J]. JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES, 2015, 70 (12): : 1461 - 1469
12345