Age-related loss of proliferative activity of human vascular smooth musclecells in culture

This work studied the proliferation activity in cultures of vascular smooth muscle cells (SMC) from individuals of different ages. The cells derived f rom arteries of 12 donors of both sexes from 45 to 91 years of age. The mai n parameter considered was the 'proliferation rate' (cells grown per day in the different culture passages) taking into account the age of the donor. No significant relationship between age of the donor and the cell life in p roliferation was found. On the contrary, the mean time of passage duration fdr reaching the maximum of proliferation as well as its 'efficiency' (maxi mum of proliferation rate registered/mean time of passage duration) show a statistically significant dependence on the age of the donor. Furthermore, the proliferation rate measured in each passage is statistically significan t related to donor age. The regressions obtained show a similar negative sl ope (VC 4%). Considering the first five culture passages, the regression cr osses the x-axis at the age of 105.6 +/- 11.7 years. This age in which no p roliferative activity of human SMC would be expected lies near the limit of maximum life potential for human beings. Our results suggest that with adv ancing donor age there is an increasing number of senescent SMC either prim arily transferred or appeared in the culture. Vascular SMC of individuals w hose life is near the end would almost be all senescent and therefore show extremely low proliferation rates in the culture. If the proliferative acti vity of arterial SMC is a condition for atherogenesis, the proportion of se nescent cells would be inversely related to the propensity of developing th e atheroma because of the inability of these cells to divide. (C) 1999 Else vier Science Ireland Ltd. All rights reserved.