Abstract
An N-glycomic analysis of plasma proteins was performed in Japanese semisupercentenarians (SSCs) (mean 106.7 years), aged controls (mean 71.6 years), and young controls (mean 30.2 years) by liquid chromatography/mass spectrometry (LC/MS) using a graphitized carbon column. Characteristic N-glycans in SSCs were discriminated using a multivariate analysis; orthogonal projections to latent structures (O-PLS). The results obtained showed that multi-branched and highly sialylated N-glycans as well as agalacto- and/or bisecting N-glycans were increased in SSCs, while biantennary N-glycans were decreased. Since multi-branched and highly sialylated N-glycans have been implicated 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 elevated in SSCs. These results suggested that responses to inflammation may 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 were associated with extreme longevity and healthy aging in humans.
Highlights
Aging is not caused by a single factor or process; it is modulated by various genetic and environmental factors such as oxidative stress and lifestyle
Sodium borohydride-reduced N-glycans from each sample were analyzed by Liquid chromatography/multiple stage mass spectrometry (LC/MSn) in the positive ion mode and negative ion mode
N-glycan structures were deduced on the basis of the accurate mass obtained by FTMS and assignments of fragment ions observed in mass spectrometry (MS)/MS, MS/MS/MS, and MS/MS/MS/MS spectra, resulting in 32 and 18 N-glycans containing multiple isomers being identified in the positive and negative ion modes, respectively (Fig 1)
Summary
Aging is not caused by a single factor or process; it is modulated by various genetic and environmental factors such as oxidative stress and lifestyle. The mechanisms underlying the aging process currently remain unclear [1]. Semisupercentenarians (SSCs; older than 105 years) are regarded as a model of human longevity because they have aged successfully [2]. Analyses of SSCs are expected to assist in elucidating the human aging process. We have physiologically and biochemically analyzed SSCs, and demonstrated that the content of oxidative stress-related proteins in the plasma of SSCs was altered from a young age [3].
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