Many theories have been put forth to explain the mechanisms of aging, but at the present time the basic underlying biological mechanisms are unknown. The immune system has an important, perhaps crucial, function in the aging process. The long range goal of this project is to study the genetic basis for cellular aging in the immune system. Emphasis will be on the role of the H-2 gene complex in lymphocyte aging. The grant will focus on two mouse strains, the long-lived C57BL/6J (H-2b) strain and the short-lived A/J (H-2a) strain. Two types of chimeric mice will be produced to study lymphocytes from the short-lived strain and the long-lived strain in the environment of a single animal. Allophenic mice (primary chimeras) and bone marrow chimeras (secondary chimeras) will be produced and bled at two month intervals. The proportion of long-lived vs. short-lived lymphocytes will be determined by H-2 typing and the hypothesis that overall lifespan is determined by the percentage of lymphocytes from the long-lived strain will be tested. An Aged Mouse Colony will be produced from the C57BL/6J (P1) and A/J (P2) mouse strains. P1, P2, F1, F2 and backcross mice from the Aged Mouse Colony will be analyzed for lifespan and H-2 haplotype to test for linkage of gene(s) determining lifespan with the H-2 complex. Lymphocytes from animals in the Aged Mouse Colony will be used to quantitate the amount of H-2 and Ia antigens, at the protein and mRNA levels, as a function of age. Preliminary data has suggested that the amount of H-2 (Kk) protein increases on lymphocytes from the A strain with age. The hypothesis, that there is an optimal level of cell surface H-2 antigens on lymphocytes, necessary for optimal immune function, will be tested. Too high a concentration of H-2 antigens on the cell surface of aged animals may be as deleterious to immune function as too low a concentration in young animals.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG002440-09
Application #
3114444
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1985-09-01
Project End
1991-08-31
Budget Start
1989-09-01
Budget End
1991-08-31
Support Year
9
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Northeastern University
Department
Type
Schools of Arts and Sciences
DUNS #
039318308
City
Boston
State
MA
Country
United States
Zip Code
02115
Assounga, Alain G; Warner, Carol M (2005) Memory lymphocytes of young and old C57BL/6 mice express high levels of class I major histocompatibility complex (H-2 Kb) protein. Growth Dev Aging 69:59-66
Assounga, Alain G; Warner, Carol M (2004) Transcription of major histocompatibility complex class I (Kb) and transporter associated with antigen processing 1 and 2 genes is up-regulated with age. Immunology 113:378-83
He, Xue Ying; Wen, Guang Yeong; Merz, George et al. (2002) Abundant type 10 17 beta-hydroxysteroid dehydrogenase in the hippocampus of mouse Alzheimer's disease model. Brain Res Mol Brain Res 99:46-53
Armstrong, M J; Janick-Buckner, D; Harvey, N et al. (1993) Lymphocyte aging in bone marrow chimeras. Growth Dev Aging 57:251-60
Armstrong, M J; Warner, C M (1992) Expression of phosphatidylinositol-dependent phospholipase C sensitive Qa-2 antigen is increased on peripheral blood lymphocytes of aging mice. Growth Dev Aging 56:225-36
Janick-Buckner, D; Briggs, C J; Meyer, T E et al. (1991) Major histocompatibility complex antigen expression on lymphocytes from aging strain A mice. Growth Dev Aging 55:53-62
Warner, C M (1986) Genetic manipulation of the major histocompatibility complex. J Anim Sci 63:279-87
Warner, C M; Briggs, C J; Meyer, T E et al. (1985) Lymphocyte aging in allophenic mice. Exp Gerontol 20:35-45
Warner, C M; Briggs, C J; Balinsky, D et al. (1985) Glucose phosphate isomerase activity in C57BL/6 and a mice of different ages. Gerontology 31:315-20
Warner, C M; Meyer, T E; Balinsky, D et al. (1985) Variations in the amount of glucose phosphate isomerase in lymphocytes and erythrocytes from A/J and C57BL/6J mice. Biochem Genet 23:815-25