Metabolic signatures of extreme longevity in northern Italian centenarians reveal a complex remodeling of lipids, amino acids, and gut microbiota metabolism
Language: 
English
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.

Author(s): 
Collino, Sebastiano
Montoliu, Ivan
Martin, FranÁois-Pierre J.
Scherer, Max
Mari, Daniela
Salvioli, Stefano
Bucci, Laura
Ostan, Rita
Monti, Daniela
Biagi, Elena
Brigidi, Patrizia
Franceschi, Claudio
Rezzi, Serge
Item Type: 
Journal Article
Publication Title: 
PloS One
Journal Abbreviation: 
PLoS ONE
Publication Date: 
2013
Publication Year: 
2013
Pages: 
e56564
Volume: 
8
Issue: 
3
ISSN: 
1932-6203
DOI: 
10.1371/journal.pone.0056564
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 23483888 PMCID: PMC3590212

Turabian/Chicago Citation

Sebastiano Collino, Ivan Montoliu, FranÁois-Pierre J. Martin, Max Scherer, Daniela Mari, Stefano Salvioli, Laura Bucci, Rita Ostan, Daniela Monti, Elena Biagi, Patrizia Brigidi, Claudio Franceschi and Serge Rezzi. 2013. "Metabolic signatures of extreme longevity in northern Italian centenarians reveal a complex remodeling of lipids, amino acids, and gut microbiota metabolism." PloS One 8: 3: e56564. 10.1371/journal.pone.0056564.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1371/journal.pone.0056564 | issn = 1932-6203 | volume = 8 | pages = e56564 | last = Collino | first = Sebastiano | coauthors = Montoliu, Ivan, Martin, FranÁois-Pierre J., Scherer, Max, Mari, Daniela, Salvioli, Stefano, Bucci, Laura, Ostan, Rita, Monti, Daniela, Biagi, Elena, Brigidi, Patrizia, Franceschi, Claudio, Rezzi, Serge | title = Metabolic signatures of extreme longevity in northern Italian centenarians reveal a complex remodeling of lipids, amino acids, and gut microbiota metabolism | journal = PloS One | date = 2013 | pmid = | pmc = }} </ref>