Alterations in molecular status of plasma fibronectin associated with aging of normal human individuals

• Age-dependent progressive modifications of fibronectin molecular status
• Increasing epitope expressions of some fibronectin domains with aging subjects
• Lower expression of α2,6-linked sialic acid on fibronectin
• Quantitative increase of the high-molecular fibronectin forms
• Conformational structural rearrangements of plasma fibronectin with subject age

ObjectivesSenescence, progressive deterioration of many bodily functions might be associated with age-dependent alterations of plasma fibronectin (FN) molecular status (i.e., domain, glycotope, and molecular form expressions).Design and methodsFN molecular status was analyzed in 127 plasma samples of healthy individuals in groups of newborns, and subjects aged 3–14, 15–39, 41–59, and 60–82 years by FN-ELISA, lectin-FN-ELISA, and immunoblotting using a set of domain-specific monoclonal antibodies, specific lectins, and monoclonal antibody to FN, respectively.ResultsDuring the first four decades of human life the levels of cell-binding-, carboxyl-terminal-, collagen-, heparin-, and fibrin-domains of plasma FN gradually increased.In subjects aged up to 82 years the cell-binding and carboxyl-terminal FN domain concentrations did not change, while the heparin, fibrin, and collagen domains significantly increased.The relative reactivity of plasma FN with Maackia amurensis lectin, specific to α2,3-linked sialic acid, significantly decreased after birth, reaching a stable level in the subsequent life period, whereas with Sambucus nigra lectin, specific to α2,6-linked sialic acid, it significantly decreased in the 60–82 year old group. Moreover, the appearance of 280-kDa and 320-kDa FN bands, absent in young and mature healthy individuals, was found in the groups of 41–59 and 60–82 year olds.ConclusionsThe alterations of FN molecular status throughout growth, maturation and senescence might be associated not only with disturbances in the balance of FN production rate and degradation, but concomitantly with conformational rearrangements of FN and its engagement in age-related vascular remodeling processes.