Characteristic glycopeptides associated with extreme human longevity identified through plasma glycoproteomics

Yuri Miura, Noritaka Hashii, Yuki Ohta, Yoko Itakura, Hiroki Tsumoto, Junya Suzuki, Daisuke Takakura, Yukiko Abe, Yasumichi Arai, Masashi Toyoda, Nana Kawasaki, Nobuyoshi Hirose, Tamao Endo

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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.

Original languageEnglish
Pages (from-to)1462-1471
Number of pages10
JournalBiochimica et Biophysica Acta - General Subjects
Volume1862
Issue number6
DOIs
Publication statusPublished - 2018 Jun 1

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Keywords

  • LC/MS
  • Lectin microarray
  • Longevity
  • N-glycosylation
  • Semi-supercentenarian

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this

Miura, Y., Hashii, N., Ohta, Y., Itakura, Y., Tsumoto, H., Suzuki, J., Takakura, D., Abe, Y., Arai, Y., Toyoda, M., Kawasaki, N., Hirose, N., & Endo, T. (2018). Characteristic glycopeptides associated with extreme human longevity identified through plasma glycoproteomics. Biochimica et Biophysica Acta - General Subjects, 1862(6), 1462-1471. https://doi.org/10.1016/j.bbagen.2018.03.025