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A glycomic study on semisupercentenarians for healthy aging and extreme longevity

Yuri Miura, Ph.D.  /  Theme Leader (Proteome)

Tamao Endo, Ph.D.  /  Former Deputy Director

The number of elderly citizens is markedly increasing worldwide, and will pose serious challenges in this century. High demands related to the maintenance and promotion of good health for the aged are expected. Semisupercentenarians (SSCs; older than 105 years) are regarded as a model of human longevity because they have aged successfully. Therefore, analyses of SSCs will assist in the investigation of factors important for healthy aging in humans.
The structures of glycans attached to proteins possess a number of positional isomers and anomeric configurations, which result in strong diversity and heterogeneity. Since glycosylation is affected by physiological and pathological conditions, glycan structures have the potential to become good targets and biomarkers for monitoring health conditions including aging. We herein examined alterations in plasma N-glycans in SSCs and younger people and reported the implications of N-glycans for successful aging.
An N-glycomic analysis of plasma proteins was performed in SSCs (mean 106.7 years), aged controls (mean 71.6 years), and young controls (mean 30.2 years) using liquid chromatography/mass spectrometry (LC/MS). Characteristic N-glycans in SSCs were discriminated using a multivariate analysis. The results obtained showed that multi-branched and highly sialylated N-glycans were abundant in SSCs. Since multi-branched and highly sialylated N-glycans are known to be involved in anti-inflammatory activities, these changes may play a role in the enhanced chronic inflammation observed in SSCs. The levels of inflammatory proteins, such as CRP, adiponectin, IL-6, and TNF-α, were also elevated in SSCs. These results suggest that responses to inflammation play an important role in extreme longevity and healthy aging in humans. This is the first study to show that the N-glycans of plasma proteins are associated with healthy aging in humans. The implications of these glycan alterations may provide new insights into extreme longevity.

1. Miura, Y., Hashii, N., Tsumoto, H., Takakura, D., Ohta, Y., Abe, Y., Arai, Y., Kawasaki, N., Hirose, N., Endo, T., on behalf of SONIC (Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians): Change in N-glycosylation of plasma proteins in Japanese semisupercentenarians, PLoS One, 10, e0142645, (2015)
2. Miura, Y., Sato, Y., Arai, Y., Abe, Y., Takayama, M., Toda, T., Hirose, N., Endo, T.: Proteomic analysis of plasma proteins in Japanese semisuper centenarians. Exp. Gerontol. 46, 81-85, (2011)