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

Characteristic glycopeptides associated with extreme human longevity identified through plasma glycoproteomics.

Author information

1
Research Team for Mechanism of Aging, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173-0015, Japan.
2
Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, 3-25-26 Tono-machi, Kawasaki-ku, Kawasaki-shi 210-9501, Kanagawa, Japan.
3
Research Team for Geriatric Medicine, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173-0015, Japan.
4
Center for Supercentenarian Medical Research, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582, Japan.
5
Research Team for Mechanism of Aging, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173-0015, Japan. Electronic address: endo@tmig.or.jp.

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

PMID:
29580922
DOI:
10.1016/j.bbagen.2018.03.025
[Indexed for MEDLINE]

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