Serum profiling of healthy aging identifies phospho- and sphingolipid species as markers of human longevity

Abstract

As centenarians well represent the model of healthy aging, there are many important implications in revealing the underlying molecular mechanisms behind such successful aging. By combining NMR metabonomics and shot-gun lipidomics in serum we analyzed metabolome and lipidome composition of a group of centenarians with respect to elderly individuals. Specifically, NMR metabonomics profiling of serum revealed that centenarians are characterized by a metabolic phenotype distinct from that of elderly subjects, in particular regarding amino acids and lipid species. Shot- gun lipidomics approach displays unique changes in lipids biosynthesis in centenarians, with 41 differently abundant lipid species with respect to elderly subjects. These findings reveal phospho/sphingolipids as putative markers and biological modulators of healthy aging, in humans. Considering the particular actions of these metabolites, these data are suggestive of a better counteractive antioxidant capacity and a well-developed membrane lipid remodelling process in the healthy aging phenotype.

Figure 1

Bar plots representing differences in serum markers of longevity as per ¹H-NMR. All significantly regulated metabolites and statistical changes are listed in Table S2.

Figure 2

Differences in mean (μM) standardized lipids value between elderly and centenarians. Represented is median value (μM) of each metabolite divided it by the IQR range of the distribution. All significantly regulated metabolites are listed in Table S5.