Protein molecular forms of insulin-like growth factor binding protein-2 change with aging

Abstract

Aging is considered to be an adaptive mechanism to altered needs of an organism and/or to altered stimuli. Plasma concentrations of insulin-like growth factor binding protein-2 (IGFBP-2) increase with age and it is generally assumed that IGFBP-2 is a negative predictor of healthy aging. The aim of this study was to examine the distribution of IGFBP-2 molecular forms in different age groups and, specifically, the relationship between IGFBP-2 and alpha-2-macroglobulin (α2M). The relative amount of monomer IGFBP-2 was the highest in young persons, making up approximately 2/3 of the total circulating IGFBP-2. This gradually decreased with age down to 1/3 of total IGFBP-2 in elderly individuals. Fragmented IGFBP-2 increased with age and contributed almost 60% to the total immunoreactive IGFBP-2 in the age group 61-80 years. IGFBP-2/α2M complexes represented 10-12% of the total IGFBP-2 in the two younger groups but half this level in the oldest group. The significance of these changes and whether they affect more IGF-dependent or independent interactions are unknown. Due to drastic proteolysis of IGFBP-2, it may be postulated that either over-release of IGFBP-2-bound IGFs causes unwanted events or IGFBP-2 fragments are able to over-stimulate cellular processes.

Keywords: Aging; Fragmentation; IGFBP-2; Protein complexes; α-2-Macroglobulin.