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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG007719-03
Application #
3118951
Study Section
Aging Review Committee (AGE)
Project Start
1988-04-01
Project End
1993-03-31
Budget Start
1990-04-01
Budget End
1991-03-31
Support Year
3
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Allegheny University of Health Sciences
Department
Type
Schools of Medicine
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19129
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Walter, R; Murasko, D M; Sierra, F (1998) T-kininogen is a biomarker of senescence in rats. Mech Ageing Dev 106:129-44
Goonewardene, I M; Murasko, D M (1995) Age-associated changes in mitogen-induced lymphoproliferation and lymphokine production in the long-lived brown-Norway rat: effect of caloric restriction. Mech Ageing Dev 83:103-16
Goonewardene, I M; Murasko, D M (1993) Age associated changes in mitogen induced proliferation and cytokine production by lymphocytes of the long-lived brown Norway rat. Mech Ageing Dev 71:199-212
Murasko, D M; Nelson, B J; Matour, D et al. (1991) Heterogeneity of changes in lymphoproliferative ability with increasing age. Exp Gerontol 26:269-79