ArticlePloS one2013
Metabolic signatures of extreme longevity in northern Italian centenarians reveal a complex remodeling of lipids, amino acids, and gut microbiota metabolism.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 150 papers, 3 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
150 citing papers in PubMed, 3 syntheses or guidelines pooled it, 269 citations in OpenAlex.
- Signatures and Clinical Significance of Amino Acid Flux in Sarcopenia: A Systematic Review and Meta-Analysis.Frontiers in endocrinology · 2021Pooled it
- Translational Potential of Metabolomics on Animal Models of Inflammatory Bowel Disease-A Systematic Critical Review.International journal of molecular sciences · 2020Pooled it
- Trans-ethnical shift of the risk genotype in the CETP I405V with longevity: a Chinese case-control study and meta-analysis.PloS one · 2013Pooled it
- Serum Concentrations of Losartan Metabolites Correlate With Improved Physical Function in a Pilot Study of Prefrail Older Adults.The journals of gerontology. Series A, Biological sciences and medical sciences · 2022Trial
- Plasma lipidome variation during the second half of the human lifespan is associated with age and sex but minimally with BMI.PloS one · 2019Trial
- Intersections of gastrointestinal dysbiosis of the gut microbiome and aging.World journal of gastrointestinal pathophysiology · 2026Review
- Taxonomic and functional remodeling of the gut microbiota during aging and implications for microbiota-derived biomarkers.World journal of microbiology & biotechnology · 2026Review
- Oral microbiome signatures predict biological age and host health.Nature communications · 2026Article
- Metabolomic signatures of extreme old age: findings from the New England Centenarian Study.GeroScience · 2026Article
- Inflammaging and Cardiovascular Risk in Old Women.High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension · 2026Review
- Longevity, Centenarians, and Lifestyle: Any ''Tips'' to Live Longer?Current nutrition reports · 2026Review
- Investigating a Systematic and Widespread Misidentification in the Metabolic Profiling Literature: Phenylacetylglutamine and Phenylacetylglycine Signal Misassignment in Proton NMR Spectra of Human and Rodent Urine.Analytical chemistry · 2025Article
- METABOLOMIC SIGNATURES OF EXTREME OLD AGE: FINDINGS FROM THE NEW ENGLAND CENTENARIAN STUDY.bioRxiv : the preprint server for biology · 2025Article
- Postbiotics: A Promising Approach to Combat Age-Related Diseases.Life (Basel, Switzerland) · 2025Review
- Immune Aging, Immunosenescence, and Inflammaging: Implications for Vaccine Response in Older Adults.Health science reports · 2025Article
- Do circulating sphingolipid species correlate with age? A study in a normoglycemic biracial population.Biogerontology · 2025Article
- Phenotypic upregulation of hexocylceramides and ether-linked phosphocholines as markers of human extreme longevity.Aging cell · 2025Article
- Centenarians-the way to healthy vascular ageing and longevity: a review from VascAgeNet.GeroScience · 2025Review
- Changes in Phenylacetylglutamine Levels Provide Add-On Value in Risk Stratification of Hypertensive Patients: A Longitudinal Cohort Study.Metabolites · 2025Article
- The plasma lipidome varies with the severity of metabolic dysfunction-associated steatotic liver disease.Lipids in health and disease · 2024Article
90 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.