We attempted to identify the effects of aging on the response of vascular smooth muscle cells (VSMCs) to injury. Rat aortas were injured by ballooning, and cell outgrowth of the aortic explants, as well as cell proliferation and apoptosis induced by 7-ketocholesterol in the culture system were compared in young (6-7 weeks) and old (40-50 weeks) rats. Explant outgrowth in uninjured rats did not differ between young and old rats. However, 14 days after balloon injury, the number of explants with outgrowth increased by a factor of four (P<0.01) in young rats, while that of the old rats did not change. Cell proliferation in cultured VSMCs also did not differ between young and old uninjured rats, but, in the injured group, proliferation doubled in young rats (P<0.01), but did not change in the older group. The rate of unadhered cells in the presence of 7-ketocholesterol (30 microM) did not differ between young and old uninjured rats. In the injured rats, however, that of young rats was lower (P<0.01) while that of older rats was higher (P<0.01). The extent of DNA fragmentation (%) after the addition of 7-ketocholesterol (30 microM) did not differ between young and old uninjured rats. In the injured groups, DNA fragmentation was lower in the young rats (P<0.01), and higher in the old ones (P<0.01), when compared to their respective controls. These results indicate that the VSMC injury responses of cell outgrowth and proliferation were more pronounced in the young, and that 7-ketocholesterol-induced apoptosis was more extensive in old rats.