Characteristic glycopeptides associated with extreme human longevity identified through plasma glycoproteomics

Biochim Biophys Acta Gen Subj. 2018 Jun;1862(6):1462-1471. doi: 10.1016/j.bbagen.2018.03.025. Epub 2018 Mar 24.

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 glycoproteomics using plasma samples of SSCs, and identified proteins and conjugated N-glycans that 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 glycopeptides to 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 glycopeptides were successfully discriminated between SSCs and controls using OPLS-DA, and indicated that tri-antennary and sialylated N-glycans of haptoglobin at Asn207 and Asn211 sites were characterized in SSCs. Sialylated glycans of haptoglobin are 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-glycans on haptoglobin at the Asn207 and Asn211 sites were abundant in SSCs and characteristic of extreme human longevity.

General significance: We found abundant glycans in SSCs, which may be associated with human longevity.

Keywords: LC/MS; Lectin microarray; Longevity; N-glycosylation; Semi-supercentenarian.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood*
  • Blood Proteins / metabolism*
  • Case-Control Studies
  • Female
  • Glycopeptides / blood*
  • Glycoproteins / blood*
  • Glycosylation
  • Humans
  • Longevity / physiology*
  • Polysaccharides / blood*
  • Proteomics / methods*
  • Young Adult

Substances

  • Biomarkers
  • Blood Proteins
  • Glycopeptides
  • Glycoproteins
  • Polysaccharides