Age-Dependent Decline of In Vitro Migration (Basal and Stimulated by IGF-1 or Insulin) of Human Vascular Smooth Muscle Cells

Abstract

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.

Impact of Insulin-like Growth Factor-I on Migration, Proliferation and Akt-ERK Signaling in Early and Late-passages of Vascular Smooth Muscle Cells

“…Interestingly, evidence has indicated that suppression of these growth factors or their receptors prolongs lifespan and delays in age-associated functional decline. Our observations in which IGF-1 induces an increase in migration and proliferation of VSMCs are in line with many of the previous results [17,18] although it contradicts some of the results obtained from human SMCs [15,16]. It has been demonstrated that late passage VSMCs possess a higher proliferative capacity in response to fetal bovine serum associated with enhanced matrix metalloprotein-9 expression in comparison with young cells [20].…”

“…Rat VSMC may not be the best model reminiscent of human VSMC life cycle [15,16], which might be a major limitation of our experiments. In contrast to human VSMCs which undergo senescence after repeated cell divisions, VSMCs from rats escape senescence following repeated subculture and may be converted to permanently de-differentiated cells.…”

“…Nevertheless the impact of vascular life cycle on VSMC proliferation and migration is still unclear. Ruiz-Torres and colleagues reported that increased age induces a decline in the migratory capacity of cultured human SMC [15,16]. However, evidence from other groups has shown that SMCs from older animals possess a higher proliferative capacity than those from younger counterparts [17][18][19].…”

“…Several lines of evidence have indicated a link between migration/proliferation of VSMCs and expression of insulin-like growth factor I (IGF-1) [15,16,23,24]. IGF-1 has a wide spectrum of physiological effects including regulation of cardiac contractility, tissue remodeling, glucose metabolism, insulin-sensitivity, and lipid profile, as well as vasomotor activity [25].…”

Cellular senescence, ageing and disease

“…Another known change associated with cellular senescence is the reduced ability to migrate (Schneider and Mitsui 1976;Sandeman et al 2000;Reed et al 2000;Ruiz-Torres et al 2003). This impaired ability to migrate may be related to changes which occur to the cytoskeleton during cellular senescence (Nishio and Inoue 2005).…”