title: The role of insulin-like growth factor 1 and insulin in ageing and atherosclerosis.
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 ICF1 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 thcrefore 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.
authors.affiliation: Instituto Universitario de Investigación, Gerontológica y Metabolica University Research Institute of Ageing, Hopital la Princesa, Madrid.
authors.forename: Antonio
authors.initials: A
authors.lastname: Ruiz-Torres
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism*; D002455:Cell Division; D002465:Cell Movement; D003599:Cytoskeleton; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology
chemical_list: D007328:Insulin; D007334:Insulin-Like Growth Factor I