The role of insulinlike growth factor 1 and insulin in ageing and atherosclerosis

Antonio Ruiz-Torres

Instituto Universitario de Investigación, Gerontologica y Metabolica (University Research Institute of Ageing), Hopital de la Princesa, Diego de Leon 62, 28006 Madrid

Abstract. With advancing age insulin-like growth factor (IGF)1 blood levels decrease continuously, but with great interindividual differences. There is a relationship between the IGF1 serum concentration and biomarker behaviour, indicating that growth hormone (GH) secretion is a determinant of organismic well being and surviving in advanced age. In contrast, the secretion of insulin rises with age, which is related to both increasing body fat mass and ageing itself. In vitro insulin stimulates the proliferation, migration and collagen secretion of human vascular smooth muscle cells (SMCs). The mechanism underlying these processes mainly involves occupancy of IGF1 receptors by insulin, with the exception of migration. With advancing age of the donor, the in vitro proliferation rate and migration capacity of SMCs decreases. When insulin or IGF1 is added, there is no reversibility, so that there is no recovery to the values of SMCs from young donors. The blockade of Ca2+ channels by diltiazem inhibits the in vitro stimulation by IGF1 and insulin on SMC proliferation and migration. We conclude that the acceleration of ageing is related to the decline of IGF1 in such a manner that ageing rates progress as GH secretion diminishes. Biomarkers are affected correspondingly. The role of insulin in atherogenesis is related to hyperinsulinaemia, but the increase in insulin secretion belongs to the process of ageing regulation. Nevertheless, the effect of insulin in changing the phenotype of SMCs is atherogenic. Diltiazem may therefore act as an antiatherogenic agent. In advanced age the risk of atherogenesis decreases because of lowered propensity of SMCs to proliferate and migrate, which is probably due to a greater proportion of senescent cells.

2002 Endocrine facets of ageing. Wiley, Chichester (Novartis Foundation Symposium 242) p 143-160

After reaching a maximum level at the end of the puberty, insulin-like growth factor 1 (IGF1) blood levels decline, indicating that the genetic programme of growth and differentiation has finished and adulthood has begun. The involution of the organism appears simultaneously with a decrease of IGF1 levels and growth hormone (GH) secretion (Iranmanesh & Veldhuis 1992, Vahl et al 1996). From a gerontological point of view, it is not possible to distinguish the signs of the involutive process and those of ageing. For this reason, the continuous decline of IGF1 secretion may be considered a marker of biological ageing.

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