Abstract
Calorie restriction (CR) is known to delay the aging process in rodents and is postulated to act by decreasing free radical generation and increasing antioxidant enzyme activity. The present study was designed to investigate the effect of CR and age on oxidative stress‐induced apoptosis and associated changes in the levels of TNF‐α, and Bcl‐2 in splenic T lymphocytes. Ad libitum (AL)‐ or CR‐fed C57BL/6J mice were sacrificed either at 6 (young) or 18 (old) months and splenic lymphocytes were incubated with or without 25 μM H~2~O~2~ to induce apoptosis. Apoptosis increased with age in cells of AL‐fed mice incubated with H~2~O~2~. CR prevented this rise in apoptosis in total splenic lymphocytes and in CD4^+^ and CD8^+^ T lymphocyte subsets either with or without H~2~O~2~. Free radicals increased and mitochondrial membrane potential decreased in aged mice. CR prevented these changes and also prevented the age‐associated increase in TNF‐α and loss of Bcl‐2 in total splenic lymphocytes and in CD4^+^ and CD8^+^ lymphocyte subsets. In summary, lymphocytes in aged AL‐fed mice were much more susceptible to oxidative stress‐induced apoptosis whereas CR normalized apoptosis by preventing the increase in TNF‐α and the decrease in Bcl‐2 associated with aging. Microsc. Res. Tech. 59:282–292, 2002. © 2002 Wiley‐Liss, Inc.