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

被引:226
作者
Collino, Sebastiano [1 ]
Montoliu, Ivan [2 ]
Martin, Francois-Pierre J. [1 ]
Scherer, Max [1 ]
Mari, Daniela [3 ,4 ]
Salvioli, Stefano [5 ,6 ]
Bucci, Laura [5 ,6 ]
Ostan, Rita [5 ,6 ]
Monti, Daniela [7 ]
Biagi, Elena [8 ]
Brigidi, Patrizia [8 ]
Franceschi, Claudio [5 ,6 ]
Rezzi, Serge [1 ]
机构
[1] Nestle Inst Hlth Sci SA, Prote & Metabon, Lausanne, Switzerland
[2] Nestec Ltd, Appl Math, Nestle Res Ctr, Lausanne, Switzerland
[3] Univ Milan, Dept Med Sci, Milan, Italy
[4] Geriatr Unit Ca Grande Fdn Maggiore Policlin Hosp, Milan, Italy
[5] Univ Bologna, Dept Expt Pathol, I-40126 Bologna, Italy
[6] Univ Bologna, Interdept Ctr L Galvani, Bologna, Italy
[7] Univ Florence, Dept Expt Pathol & Oncol, Florence, Italy
[8] Univ Bologna, Dept Pharmaceut Sci, I-40126 Bologna, Italy
关键词
LOW-DENSITY LIPOPROTEINS; EPOXYEICOSATRIENOIC ACIDS; RHEUMATOID-ARTHRITIS; CALORIC RESTRICTION; CROHNS-DISEASE; FATTY-ACIDS; PLASMA; SPECTROSCOPY; POPULATION; IDENTIFICATION;
D O I
10.1371/journal.pone.0056564
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
The aging phenotype in humans has been thoroughly studied but a detailed metabolic profiling capable of shading light on the underpinning biological processes of longevity is still missing. Here using a combined metabonomics approach compromising holistic 1 H-NMR profiling and targeted MS approaches, we report for the first time the metabolic phenotype of longevity in a well characterized human aging cohort compromising mostly female centenarians, elderly, and young individuals. With increasing age, targeted MS profiling of blood serum displayed a marked decrease in tryptophan concentration, while an unique alteration of specific glycerophospholipids and sphingolipids are seen in the longevity phenotype. We hypothesized that the overall lipidome changes specific to longevity putatively reflect centenarians' unique capacity to adapt/respond to the accumulating oxidative and chronic inflammatory conditions characteristic of their extreme aging phenotype. Our data in centenarians support promotion of cellular detoxification mechanisms through specific modulation of the arachidonic acid metabolic cascade as we underpinned increased concentration of 8,9-EpETrE, suggesting enhanced cytochrome P450 (CYP) enzyme activity. Such effective mechanism might result in the activation of an anti-oxidative response, as displayed by decreased circulating levels of 9-HODE and 9-oxoODE, markers of lipid peroxidation and oxidative products of linoleic acid. Lastly, we also revealed that the longevity process deeply affects the structure and composition of the human gut microbiota as shown by the increased extrection of phenylacetylglutamine (PAG) and p-cresol sulfate (PCS) in urine of centenarians. Together, our novel approach in this representative Italian longevity cohort support the hypothesis that a complex remodeling of lipid, amino acid metabolism, and of gut microbiota functionality are key regulatory processes marking exceptional longevity in humans.
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页数:12
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