Characteristic glycopeptides associated with extreme human longevity identified through plasma glycoproteomics

Abstract Background Glycosylation is highly susceptible to changes of the physiological conditions, and accordingly, is a potential biomarker associated with several diseases and/or longevity. Semi-supercentenarians (SSCs; older than 105 years) are thought to be a model of human longevity. Thus, we performed glycoproteomicsusing plasma samples of SSCs, and identified proteins and conjugated N - glycansthat are characteristic of extreme human longevity. Methods Plasma proteins from Japanese semi-supercentenarians (SSCs, 106–109 years), aged controls (70–88 years), and young controls (20–38 years) were analysed by using lectin microarrays and liquid chromatography/mass spectrometry (LC/MS). Peak area ratios of glycopeptidesto corresponding normalising peptides were subjected to orthogonal projections to latent structures discriminant analysis ( OPLS-DA). Furthermore, plasma levels of clinical biomarkers were measured. Results We found two lectins such as Phaseolus vulgaris, and Erythrina cristagalli(ECA), of which protein binding were characteristically increased in SSCs. Peak area ratios of ECA-enriched glycopeptideswere successfully discriminated between SSCs and controls using OPLS-DA, and indicated that tri-antennary and sialylated N - glycansof haptoglobinat Asn207 and Asn211 sites were characterized in SSCs. Sialylated glycansof haptoglobinare a potential biomarker of several diseases, such as hepatocellular carcinoma, liver cirrhosis, and IgA-nephritis. However, the SSCs analysed here did not suffer from these diseases. Conclusions Tri-antennary and sialylated N - glycanson haptoglobinat the Asn207 and Asn211 sites were abundant in SSCs and characteristic of extreme human longevity. General significance We found abundant glycansin SSCs, which may be associated with human longevity.