Inflamm-aging, that is the age-associated inflammatory status, is considered one of the most striking consequences of immunosenescence, as it is believed to be linked to the majority of age-associated diseases sharing an inflammatory basis. Nevertheless, evidence is emerging that inflamm-aging is at least in part independent from immunological stimuli. Moreover, centenarians who avoided or delayed major inflammatory diseases display markers of inflammation. In this paper we proposed a reappraisal of the concept of inflamm-aging, suggesting that its pathological effects can be independent from the total amount of pro-inflammatory mediators, but they would be rather associated with the anatomical district and type of cells where they are produced and where they primarily act.

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BackgroundGlycosylation, i.e the enzymatic addition of oligosaccharides (or glycans) to proteins and lipids, known as glycosylation, is one of the most common co-/posttranslational modifications of proteins. Many important biological roles of glycoproteins are modulated by N-linked oligosaccharides. As glucose levels can affect the pathways leading to glycosylation of proteins, we investigated whether metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM), pathological conditions characterized by altered glucose levels, are associated with specific modifications in serum N-glycome.MethodsWe enrolled in the study 562 patients with Type 2 Diabetes Mellitus (T2DM) (mean age 65.6±8.2 years) and 599 healthy control subjects (CTRs) (mean age, 58.5±12.4 years). N-glycome was evaluated in serum glycoproteins.ResultsWe found significant changes in N-glycan composition in the sera of T2DM patients. In particular, α(1,6)-linked arm monogalactosylated, core-fucosylated diantennary N-glycans (NG1(6)A2F) were significantly reduced in T2DM compared with CTR subjects. Importantly, they were equally reduced in diabetic patients with and without complications (P<0.001) compared with CTRs. Macro vascular-complications were found to be related with decreased levels of NG1(6)A2F. In addition, NG1(6)A2F and NG1(3)A2F, identifying, respectively, monogalactosylated N-glycans with α(1,6)- and α(1,3)-antennary galactosylation, resulted strongly correlated with most MS parameters. The plasmatic levels of these two glycans were lower in T2DM as compared to healthy controls, and even lower in patients with complications and MS, that is the extreme “unhealthy” phenotype (T2DM+ with MS).ConclusionsImbalance of glycosyltransferases, glycosidases and sugar nucleotide donor levels is able to cause the structural changes evidenced by our findings. Serum N-glycan profiles are thus sensitive to the presence of diabetes and MS. Serum N-glycan levels could therefore provide a non-invasive alternative marker for T2DM and MS.

In recent years, plasma N-glycans have emerged as biomarkers for health and disease. Here, we studied N-glycomic changes in Down Syndrome (DS). Because of the progeroid phenotype of DS, we focused on the dissection of syndrome- and aging-associated glycomic changes, as well as the interaction thereof. We analyzed the plasma N-glycome of 76 DS persons, 37 siblings (DSS), and 42 mothers (DSM) of DS persons by DNA-sequencer-aided, fluorophore-assisted-carbohydrate-electrophoresis, as well as by matrix-assisted laser desorption ionization-time-of-flight-mass spectrometry (MALDI-TOF-MS). The results showed an overall decrease of galactosylation and α2,3 sialylation, a concomitant increase of the level of fucosylated N-glycans as well as of monogalactosylated diantennary N-glycans in DS, while the GlycoAgeTest and the ratio of the two core-fucosylated, monogalactosylated diantennary isomers (galactose positioned on α1,6 arm versus α1,3 arm) were the strongest DS discriminators. Hypogalactosylation is a characteristic of both DS and aging of control individuals. A decrease in α2,3-sialylated species is also common to DS and aging of controls. However, regarding to α2,6-sialylated tri- and tetragalactosylated N-glycan species, we found those to be lowered in DS but showed an increase with age in the same persons, while these glycans were not affected by aging in control individuals. In conclusion, we identified specific glycomic changes associated with DS, aging in DS, as well as aging in controls, identifying glycomic features in line with accelerated aging in DS. Notably, our data demonstrate an aging phenotype in DS which only in part overlaps with aging in controls but reveals DS-specificity.

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