Project Number: 1950-51000-067-01-S
Project Type: Specific Cooperative Agreement
Start Date: Jan 23, 2009
End Date: Jan 22, 2014
1. Determine the effect and mechanisms of food components and their interaction with age on immune function and infectious diseases. a) Determine the mechanisms of Vitamin E-induced enhancement of T cell function in the aged with focus on early activation signaling and membrane related events. b) Determine the contribution of polymorphisms at cytokine genes to heterogeneity of vitamin E-induced effects on cytokine production and resistance to respiratory infections. 2. Determine the effect of reducing caloric intake on the immune response of humans. 3. Determine the effect and mechanisms of food components and their interaction with age on immune function and infectious diseases.
T cell function declines with age resulting in higher incidence of infections in the elderly. We showed that vitamin E (E) supplementation enhances T cell function in the aged. In Objective 1-A, we will test the hypothesis that T cell receptor (TCR)-induced signalosomes(combination of protein and lipids that are formed at the site of T cell and antigen presenting cells) exhibit age- and vitamin E (E)-related differences in their patterns of protein and lipid recruitment. We will identify qualitative and quantitative age- and E-related differences in the protein and lipid composition of signalosomes using an enhanced magnetic immunoisolation procedure and highly sensitive and quantitative proteomics and lipidomics methods. In objective 1-B, we will test the hypothesis that higher frequencies of specific cytokine polymorphisms contribute to incidence and severity of respiratory infection (RI) in the aged and that the effect of E on RI is dependent on cytokine genotype. This will be tested using data and DNA samples collected from a 1-year randomized, doubleblind, controlled (RTC) study of E supplementation in elderly. In Objective 2 we will test the hypothesis that a long- term calorie restriction (CR) intervention in humans will enhance T cell-mediated function and that the CR- mediated effect is due to intrinsic changes in T cells and/or a reduction in prostaglandin PGE2 production. This hypothesis will be tested utilizing subjects enrolled in the NIA- supported multi-center RTC, CALERIE Phase 2 and determining the effect of CR on T cell subsets proliferation, and intra- and extra-cellular cytokine, and PGE2 levels before, and following 1 and 2 years of 25% CR. These studies will help develop effective strategies to improve the immune response in the elderly.