Immune and Neurologic Parameters as Biomarkers of Aging

Murasko, Donna

Abstract

The purpose of this study is to determine whether or not changes in immune parameters in conjunction with changes in the neurological system, can be used to determine the """"""""physiologic age"""""""" of an individual. This goal will be accomplished by: 1. determining the level of expression of five immune parameters in splenic lymphocytes throughout the lifespan of one strain of rat. The immune parameters include: a) mitogen induced lymphocyte proliferation at both optimum and supraoptimum mitogen concentrations; b) T cell subpopulations before and after mitogen stimulation; c) expression of lymphocyte activation markers during mitogen stimulation; d) production of lymphokines during mitogen stimulation; and e) lymphoproliferation after addition of exogenous lymphokines. 2. determining the level of two markers of neurological status simultaneously with the immune evaluations. Specifically, the level of calcium-activated neutral proteases (CANP's), whose primary substrate is intermediate filaments, and their inhibitors, calpistatins, will be examined in astrocytes. 3. correlating the changes observed in CANP's and calpistatins in astrocytes with those observed in erythrocytes. This will allow simple and non-invasive evaluation of these neurological markers. 4. utilizing multivariate analyses to develop a """"""""predictive equation of age"""""""" based on the immune parameters and the neurological markers evaluated in erythrocytes. 5. repeating the above evaluations with animals fed caloric restricted diets to determine if the same group of parameters are the best predictors of age. 6. repeating the above evaluations with new sets of normal and dietary restricted animals of the same strain to evaluated the accuracy of the predictive equation. 7. extending the validation to another strain of rats and then to strains of mice. This is necessary to determine the universality of the predictive equation. The data obtained during the five year period of the study will allow definitive conclusions regarding whether or not: 1) any immune parameters alone or in conjunction with markers of neurological status, are accurate predictors of physiological age and 2) the same parameters predict age equally well in at least two species of animals. An answer of """"""""yes"""""""" to both of these questions will suggest that the predictive equation of physiologic age should be useful in humans.