30% of heart cells may be lost with advancing age through increased cell death due to apoptosis and necrosis. Previously, we demonstrated that exercise training (ET) attenuated age-induced increases in mitochondria-mediated apoptosis. Aging increases inflammatory cytokine levels in many tissues including heart. We hypothesized that ET would ameliorate age-induced changes in fas/cytokine-mediated apoptotic signaling in the left ventricle. 3 and 24 mo. old Fischer-344 rats were assigned to young sedentary (YS), young exercise (YE), old sedentary (OS), and old exercise (OE) groups. ET groups ran on a treadmill for 60 min/day, 5 d/wk for additional 12 wks. Fas, p-FADD (phosphorylated fas-associating death domain), pro-caspase-8, cleaved caspase-8, and ARC (apoptosis repressor with caspases recruitment domain) protein expression in the left ventricle were measured by Western blot. Pro-caspase-8 (+117%) and cleaved caspase-8 (+140%) levels were markedly elevated with aging, whereas cleaved caspase-8 was reduced by ET (-54%) in old rats. p-FADD levels increased with aging, but there were no training effects on p-FADD in old groups. Fas was not affected by aging or ET. ARC was not affected by age or ET, but a small trend (+10%) existed in OE compared with YS. Our results indicate that 12 weeks of treadmill exercise training attenuates caspase-8 cleavage, but are not consistent with a significant contribution by upstream fas/cytokine regulators tested. Supported by Texas Affiliate of the American Heart Association (GIA # 0555064Y)