Caloric restriction responses can maintain immune responses during aging (47.14)

Abstract

Abstract Age-related defects accumulate in both the innate and adaptive arms of immunity to generate a state of immune deficiency. Our laboratory has previously shown a decrease in immune responses in aged mice compared to younger mice in the context of OX40 costimulation. This loss of immunity during aging underscores the need for simple approaches to boost immunity in older individuals. We hypothesize that immune responses in the context of OX40 activation or blockade of CTLA-4 in older mice can be restored and/or maintained through caloric restriction (CR) or dietary supplementation with a CR mimetic. Two CR dietary regimens were used to determine if immunity in old immune-compromised mice could be restored and if immunity could be maintained during aging. In addition mice were fed diets that were formulated with resveratrol (100 ppm), a CR mimetic. Tumor immune responses and Ag-specific T cell responses in these mice were then assessed and compared to young mice and the appropriate dietary controls. Our results demonstrate that caloric restriction cannot restore immune function in old mice. However, CR or resveratrol dietary supplementation initiated at a young age can maintain both OX40-mediated anti-tumor immunity and T cell responses as these mice age. Thus, the induction of a caloric restriction response (via traditional CR or by a CR mimetic) appears to maintain immunological fitness and may increase the effectiveness of immune-based cancer therapies in older subjects.