Metabolic Signatures of Extreme Longevity in Northern Italian Centenarians Reveal a Complex Remodeling of Lipids, Amino Acids, and Gut Microbiota Metabolism
Open accessAbstract
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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Studies in the past decade have demonstrated that gut microbiome composition changes with age, that exceptionally long-lived individuals have a different microbiome composition from average older adults, and that certain microorganisms and the metabolites they produce are beneficial to human health.
“Studies in the past decade have demonstrated that gut microbiome composition changes with age, that exceptionally long-lived individuals have a different microbiome composition from average older adults131–133, and that certain microorganisms131,134,135 and the metabolites they produce132,134,136 are beneficial to human health.”
From Measuring biological age using omics data (2022) · cites this paper as [132]
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References 60 · Cited by 270
Research works printed but not linked: 2
- [28]Wijeyesekera A, Selman C, Barton RH, Holmes E, Nicholson JK, et al (2012) Metabotyping of long-lived mice using 1H NMR spectroscopy. J Proteome Res 11: 2224– 2235. 22225495 PMC4467904
- [47]Jira W, Spiteller G, Richter A (1997) Increased levels of lipid oxidation products in low density lipoproteins of patients suffering from rheumatoid arthritis. Chem Phys Lipids 87: 81– 89. 9219348
- Authors
- Collino, S., Montoliu, I., Martin, F.-P. J., Scherer, M., Mari, D., Salvioli, S., Bucci, L., Ostan, R., Monti, D., Biagi, E., Brigidi, P., Franceschi, C., & Rezzi, S.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- Nestlé (Switzerland) (CH)
- University of Milan (IT)
- University of Bologna (IT)
- University of Florence (IT)
- Corresponding author
- Collino, Sebastiano
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-03-06
- Volume
- 8
- Issue
- 3
- Pages
- e56564
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3590212
- OpenAlex
- W1987459626
- Cited by
- 270
- References
- 60
- Citations by year
- 2026: 10 · 2025: 12 · 2024: 31 · 2023: 18 · 2022: 26 · 2021: 35 · 2020: 23 · 2019: 16 · 2018: 14 · 2017: 23 · 2016: 17 · 2015: 18 · 2014: 19 · 2013: 8
- FWCI
- 9.26
- Type
- journal article
- Language
- en
- Update notices
- correction (2013-08-13)
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Florence Research (University of Florence) (submittedVersion, cc-by)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Ministero dell’Istruzione, dell’Università e della Ricerca (PRIN 2006)
- Università degli Studi di Firenze
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Health, Environment, Cognitive Aging
- Keywords
- exceptional longevity, centenarians, human aging, metabolic phenotypes, lipid metabolism, glycerophospholipids, sphingolipids, tryptophan, arachidonic acid metabolism, cytochrome P450, lipid peroxidation, oxidative stress, gut microbiota, phenylacetylglutamine, p-cresyl sulfate, urinary metabolites, amino acid metabolism
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Amino Acids, Child, Chromatography, Liquid, Demography, Female, Humans, Italy, Longevity, Male, Middle Aged, Magnetic Resonance Spectroscopy, Phenotype, Mass Spectrometry, Cohort Studies, Biomarkers, Eicosanoids, Gastrointestinal Tract, Lipid Metabolism, Metagenome, Metabolomics, Metabolome, Young Adult
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