Structural and functional changes of fibrinogen due to aging

Abstract

Different factors affect coagulation process. Since fibrinogen is the main coagulation factor, the influence of aging on fibrinogen structure and function was investigated in this study. Fibrinogen was isolated from plasma obtained from healthy persons in the age range 21–83 and examined. Lectin microarray analysis demonstrated increased glycosylation of fibrinogen due to aging, with predominant increase in high-mannose or hybrid type N-glycans, as well as tri-/tetraantennary complex N-glycans with greater content of galactose and N-acetylglucosamine residues. Spectrofluorimetric analysis indicated that fibrinogen molecules have more densely packed structure, but there are no additional advanced glycation end products with increasing age. According to the results of functional analysis, fibrinogen molecules isolated from older persons exhibited reduced clotting time, with significant positive correlation with age, but there were no differences in clotting speed, maximal optical density of fibrin clot, diameter of fibrin fibres, fibrin porosity or reactivity with the insulin-like growth factor binding protein 1. Glycosylation changes of fibrinogen in healthy aging most likely affect its structure and function, namely clotting time. Structural and functional studies of proteins in relation to healthy aging contribute to deeper understanding of mechanisms responsible for longevity.