Distinct metabolomic signatures are associated with longevity in humans

被引：124

作者：

Cheng, Susan ^{[1
,2
,3
]}

Larson, Martin G. ^{[1
,2
,4
]}

McCabe, Elizabeth L. ^{[5
]}

Murabito, Joanne M. ^{[1
,2
,6
]}

Rhee, Eugene P. ^{[7
]}

Ho, Jennifer E. ^{[1
,2
,8
,9
]}

Jacques, Paul F. ^{[10
]}

Ghorbani, Anahita ^{[8
]}

Magnusson, Martin ^{[11
]}

Souza, Amanda L. ^{[12
]}

Deik, Amy A. ^{[12
]}

Pierce, Kerry A. ^{[12
]}

Bullock, Kevin ^{[12
]}

O'Donnell, Christopher J. ^{[1
,2
,8
,13
]}

Melander, Olle ^{[11
]}

Clish, Clary B. ^{[12
]}

Vasan, Ramachandran S. ^{[1
,2
,9
,14
]}

Gerszten, Robert E. ^{[8
,12
,15
]}

Wang, Thomas J. ^{[16
]}

机构：

[1] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA

[2] Boston Univ, Sch Med, Framingham, MA 01702 USA

[3] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA

[4] Boston Univ, Dept Math & Stat, Boston, MA 02115 USA

[5] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA

[6] Boston Univ, Sch Med, Dept Med, Div Gen Internal Med, Boston, MA 02118 USA

[7] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Renal, Boston, MA 02116 USA

[8] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02116 USA

[9] Boston Univ, Sch Med, Dept Med, Div Cardiol, Boston, MA 02118 USA

[10] Tufts Univ, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Boston, MA 02111 USA

[11] Lund Univ, Dept Clin Sci, SE-22100 Lund, Sweden

[12] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[13] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA

[14] Boston Univ, Sch Med, Dept Med, Div Prevent Med, Boston, MA 02118 USA

[15] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02116 USA

[16] Vanderbilt Univ, Div Cardiovasc Med, Nashville, TN 37232 USA

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

关键词：

MITOCHONDRIAL NADP(+)-ISOCITRATE DEHYDROGENASE; GENOME-WIDE ASSOCIATION; BILE-ACIDS; CARDIOVASCULAR HEALTH; DIETARY RESTRICTION; LIFE-SPAN; HEART; DISEASE; RISK; HYPERTROPHY;

D O I：

10.1038/ncomms7791

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Alterations in metabolism influence lifespan in experimental models, but data in humans are lacking. Here we use liquid chromatography/mass spectrometry to quantify 217 plasma metabolites and examine their relation to longevity in a large cohort of men and women followed for up to 20 years. We find that, higher concentrations of the citric acid cycle intermediate, isocitrate, and the bile acid, taurocholate, are associated with lower odds of longevity, defined as attaining 80 years of age. Higher concentrations of isocitrate, but not taurocholate, are also associated with worse cardiovascular health at baseline, as well as risk of future cardiovascular disease and death. None of the metabolites identified are associated with cancer risk. Our findings suggest that some, but not all, metabolic pathways related to human longevity are linked to the risk of common causes of death.

引用

页数：9

共 70 条

[1] Gene expression profile of long-lived Ames dwarf mice and Little mice [J].

Amador-Noguez, D ;

Yagi, K ;

Venable, S ;

Darlington, G .

AGING CELL, 2004, 3 (06) :423-441

[2]

[Anonymous], 2008, USDA NAT NUTR DAT ST

[3]

[Anonymous], NIH PUBLICATION

[4] Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake [J].

Anson, RM ;

Guo, ZH ;

de Cabo, R ;

Iyun, T ;

Rios, M ;

Hagepanos, A ;

Ingram, DK ;

Lane, MA ;

Mattson, MP .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (10) :6216-6220

[5] A metabolic view on menopause and ageing [J].

Auro, Kirsi ;

Joensuu, Anni ;

Fischer, Krista ;

Kettunen, Johannes ;

Salo, Perttu ;

Mattsson, Hannele ;

Niironen, Marjo ;

Kaprio, Jaakko ;

Eriksson, Johan G. ;

Lehtimaki, Terho ;

Raitakari, Olli ;

Jula, Antti ;

Tiitinen, Aila ;

Jauhiainen, Matti ;

Soininen, Pasi ;

Kangas, Antti J. ;

Kahonen, Mika ;

Havulinna, Aki S. ;

Ala-Korpela, Mika ;

Salomaa, Veikko ;

Metspalu, Andres ;

Perola, Markus .

NATURE COMMUNICATIONS, 2014, 5

[6] Decreased cardiac mitochondrial NADP+-isocitrate dehydrogenase activity and expression:: a marker of oxidative stress in hypertrophy development [J].

Benderdour, M ;

Charron, G ;

Comte, B ;

Ayoub, R ;

Beaudry, D ;

Foisy, S ;

deBlois, D ;

Des Rosiers, C .

AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2004, 287 (05) :H2122-H2131

[7] Cardiac mitochondrial NADP+-isocitrate dehydrogenase is inactivated through 4-hydroxynonenal adduct formation -: An event that precedes hypertrophy development [J].

Benderdour, M ;

Charron, G ;

deBlois, D ;

Comte, B ;

Des Rosiers, C .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (46) :45154-45159

[8] Deletion of the Mammalian INDY Homo log Mimics Aspects of Dietary Restriction and Protects against Adiposity and Insulin Resistance in Mice [J].

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. .

CELL METABOLISM, 2011, 14 (02) :184-195

[9] Bile acids regulate hepatic gluconeogenic genes and farnesoid X receptor via Gαi-protein-coupled receptors and the AKT pathway [J].

Cao, Risheng ;

Cronk, Zhumei Xu ;

Zha, Weibin ;

Sun, Lixin ;

Wang, Xuan ;

Fang, Youwen ;

Studer, Elaine ;

Zhou, Huiping ;

Pandak, William M. ;

Dent, Paul ;

Gil, Gregorio ;

Hylemon, Phillip B. .

JOURNAL OF LIPID RESEARCH, 2010, 51 (08) :2234-2244

[10] Metabolic Signatures of Extreme Longevity in Northern Italian Centenarians Reveal a Complex Remodeling of Lipids, Amino Acids, and Gut Microbiota Metabolism [J].

Collino, Sebastiano ;

Montoliu, Ivan ;

Martin, Francois-Pierre J. ;

Scherer, Max ;

Mari, Daniela ;

Salvioli, Stefano ;

Bucci, Laura ;

Ostan, Rita ;

Monti, Daniela ;

Biagi, Elena ;

Brigidi, Patrizia ;

Franceschi, Claudio ;

Rezzi, Serge .

PLOS ONE, 2013, 8 (03)

← 1 2 3 4 5 6 7 →