Effects of caloric restriction on age-related oxidative modifications of macromolecules and lymphocyte proliferation in rats

Decreased immune function associated with aging has been demonstrated in both humans and animals. We hypothesize that reactive oxygen species (ROS)-mediated damage to biological macromolecules may contribute to compromised immune response during aging. In this study, we compared the levels of lipid peroxidation and oxidatively modified proteins in plasma and splenocytes, and the mitogen-induced T lymphocyte proliferation in ad lib-fed (AL) and caloric restricted (CR) Fischer 344 × BNF₁ male rats at the ages of 5, 18, and 31 months. The results show that AL rats exhibit an age-related decrease in proliferative response of splenic lymphocytes to phytohemagglutinin (PHA) and concanavalin A (Con A). This functional decline in T-lymphocytes during aging is inversely correlated to the levels of both lipid peroxidation and protein carbonyl in the plasma and splenic lymphocytes. Caloric restriction, however, can partially reverse the age-dependent decrease in T lymphocyte proliferation and significantly reduce lipid peroxidation and protein carbonyl contents in plasma and splenocytes. The above observations support the hypothesis that the age-associated declines in immune function are related to the oxidative modification of biological macromolecules, which in turn may lead to enzyme inactivation, membrane disruption, and cell senescence. One of the mechanisms by which caloric restriction reverses declined immune function in aged rats is hypothesized to be through reduction in ROS production and thereby protection of cellular macromolecules against oxidative damage.