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Since biological aging causes a decrease in functions such as cell proliferation, we have studied the possible effect of age on the migration capacity of human vascular smooth muscle cells (SMCs). To this aim, the migration activity of cultured SMCs from arteries of male human donors ranging in age from 43-77 years was determined in a Boyden chamber, under basal conditions and after insulin-like growth factor-1 (IGF-1) or insulin stimulation. Migration activity decreased with donor age (r2 = 87%, 85%, and 78%, respectively). IGF-1 and insulin significantly reduced the age-dependent relationship observed in basal conditions, so that, comparing young with old, both IGF-1 and insulin stimulated SMC migration similarly, although the effect of age remained in absolute terms. In this article, we conclude that the age-dependent decline of migration activity--similar to what has already been shown for SMC proliferation--may be part of the biological ageing phenotype, which is not overcome by hormone stimulation.

The process of aging results in an increase in collagen in arterial walls, but the blood levels of insulin-like growth factor 1 (IGF-1) decrease remarkably as adults age. There is an almost simultaneous increase in insulin secretion, particularly in obese individuals. It is not known if, under these hormonal conditions, the enrichment of collagen in the arterial wall is due to insulin. We studied the effect of insulin on the production of collagen in vascular smooth muscle cells (VSMC) from elderly persons with high levels of insulin secretion after blocking the insulin receptors with a monoclonal antibody. Results were compared to those without insulin receptor blockage and to those with IGF-1. Despite the inhibition of ¹⁴C-glucose uptake, insulin clearly stimulated the release of procollagen III, and increased the collagen synthesis. The hydroxyproline labelling rate from ³H-proline increased to more than twice the control values. IGF-1 is a more potent effector than insulin, but the effect of insulin on the rate of collagen production became similar to IGF-1 when the specific receptors were blocked. The results indicate that under special conditions that occur with aging, insulin interacts with nonspecific receptors in VSMC, especially IGF-1, stimulating these cells to produce collagen.

Background: It is known that growth factors play a role in ageing and atherogenesis, and insulin develops mitogenic activity in vitro. Objectives: This study focusses on the pathway by which insulin induces proliferation and mobility in vascular smooth muscle cells (SMCs) compared with that of insulin-like growth factor-1 (IGF-1), because they are two basic phenomena for atherogenesis that could also help to understand the role of insulin in the ageing process. Methods: Bromodeoxyuridine DNA incorporation, chemotaxis and the appearance of membrane ruffles were measured in cultured SMCs after incubation with insulin or IGF-1 in the presence of insulin or IGF-1 receptor-blocking antibodies. Results: Insulin-induced SMC proliferation through the IGF-1 receptors; indeed, the blockade of insulin receptors does not inhibit the mitogenic influence of insulin. On the contrary, insulin-induced cell migration was inhibited by blocking the insulin receptor but not the IGF-1 receptor. Nevertheless, in less differentiated SMCs from non-confluent cultures, the migratory response was significantly higher and insulin lost its receptor specificity. It was stimulated through receptors both for insulin and IGF-1. In these cases the IGF-1 action was similar. Insulin-induced F-actin rearrangements took place through both types of receptors, but IGF-1 was a little more specific through its own receptors. Conclusion: The pathway activated by insulin to induce SMC proliferation is not different from that of IGF-1, whereas the unspecific mechanism inducing mobility in growing cells seems to be related to a higher sensitivity response. Cells with the highest mitotic activity have the highest mobility in which stimulation of receptor specificity is lost for either insulin or IGF-1. Extrapolating these results to in vivo, insulin could become relevant for inducing stabilization and also side effects in ageing.

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