CALORIC RESTRICTION AND IMMUNE SENESCENCE IN PRIMATES

Oregon Health & Science University, Portland OR

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Immune senescence is a state of diminished immune competence, manifested by reduced ability to respond to and clear pathogens and tumors, and believed to significantly contribute to morbidity and mortality in older individuals. Caloric restriction (CR) is the only intervention that consistently and significantly prolongs lifespan and delays the age-associated morbidity and mortality in experimental animals, but its mechanism of action is incompletely understood. While CR appears to be beneficial for the aging rodent immune system, its effects upon the primate immune system and its ability to reverse immune senescence are unknown. We are testing the hypothesis that CR acts to maintain T-cell subset balance and preserve T-cell responsiveness in aged RM by measuring the key immunological parameters known to be affected by aging in other species, using adult and old animals fed regular or CR diet. Specific aims examine the effects of aging and CR on T-cell subset frequencies and function;thymic output and peripheral T-cell homeostasis;and T-cell receptor (TCR) diversity amongst discrete T-cell subsets and T-cell subset gene expression patterns.