Our long term efforts have been directed towards establishing the protective effects of various dietary lipids and decreased calorie intake against the development and acceleration of autoimmune disease (AD) which causes early morbidity and mortality in aging populations. : We recently observed that feeding commonly-consumed dietary fats such as monounsaturated Lard (rich in (18:1) omega-9) or polyunsaturated (PUFA) corn oil (rich in (18:2) (omega-6) promotes AD in NZBxNZWF1 (B/W) female mice, whereas highly polyunsaturated (HUFA) omega-3 fish oil (high in (20:5) and (22:6) (omega-3) with optimum antioxidant supplement exerts a significant protection. A more dramatic effect on inhibition of AD and lengthening of life span was however noted, when we followed a combination of HUFA diet with food restriction (FR). Our working hypothesis is that increased oonsumption of PUFA promotes AD and certain malignancies by inducing elevated levels of endocrine hormones, autoantibodies and several proinflammatory cytokines. We have recently observed that protection against AD can be achieved by FR by inhibiting the rise in memory T cells (PGP-1high) which are known to produce pro-inflammatory cytokines such as IL-4, IL-5, and IL-6. Our proposed studies are therefore directed toward elucidating the immunological mechanism(s) involved in increasing the anti-inflammatory cytokines by following a well-balanced ratio of (omega-6 and o)-3 fatty acids in the diet. We therefore intend to study and compare the effects of diets containing PUFA (18:2) omega-6 and linolenic acid-containing oils such as flax seed oil (18:3 omega-3); and also continued the studies with menhaden fish oil ((omega-3), with and without FR, to define age-associated functional changes in virgin (PGP-1high) and memory (PGP-1high) T cells, B cells and macrophages (M0). Furthermore, production of anti-inflammatory (IL-2, IFN-gamma), pro-inflammatory as well as regulatory (IL-10) cytokines will also be measured by bioassays to compare lymphokine release in activated T lymphocytes and M0. This study will be further parallelled by analysis of mRNA accumulation and protein production both in young and old animals fed HUFA omega-3 and PUFA diets. Also, phospholipid composition and Ca2+ influx in T cell subsets and changes in self-reactive T cell receptor Vp regions in response to Con-A or staphylococcal enterotoxin B will be analyzed. Proposed studies should further contribute to a better understanding of the protective role of dietary factors involving lipids and calorie intake on delaying AD in mice. These findings can be applied to reducing age-related AD phenomena by appropriate long-term dietary interventions to improve the quality of life in the aging population.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
2R01AG003417-12
Application #
3114723
Study Section
Immunobiology Study Section (IMB)
Project Start
1981-09-15
Project End
1995-06-30
Budget Start
1992-08-15
Budget End
1993-06-30
Support Year
12
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Type
Schools of Medicine
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
Paulsen, Jane S; Wang, Chiachi; Duff, Kevin et al. (2010) Challenges assessing clinical endpoints in early Huntington disease. Mov Disord 25:2595-603
Venjatraman, J T; Fernandes, G (1997) Exercise, immunity and aging. Aging (Milano) 9:42-56
Fernandes, G; Chandrasekar, B; Luan, X et al. (1996) Modulation of antioxidant enzymes and programmed cell death by n-3 fatty acids. Lipids 31 Suppl:S91-6
Chandrasekar, B; McGuff, H S; Aufdermorte, T B et al. (1995) Effects of calorie restriction on transforming growth factor beta 1 and proinflammatory cytokines in murine Sjogren's syndrome. Clin Immunol Immunopathol 76:291-6
Warner, H R; Fernandes, G; Wang, E (1995) A unifying hypothesis to explain the retardation of aging and tumorigenesis by caloric restriction. J Gerontol A Biol Sci Med Sci 50:B107-9
Fernandes, G; Chandrasekar, B; Troyer, D A et al. (1995) Dietary lipids and calorie restriction affect mammary tumor incidence and gene expression in mouse mammary tumor virus/v-Ha-ras transgenic mice. Proc Natl Acad Sci U S A 92:6494-8
Troyer, D A; Chandrasekar, B; Thinnes, T et al. (1995) Effects of energy intake on type 1 plasminogen activator inhibitor levels in glomeruli of lupus-prone B/W mice. Am J Pathol 146:111-20
Chandrasekar, B; Troyer, D A; Venkatraman, J T et al. (1995) Dietary omega-3 lipids delay the onset and progression of autoimmune lupus nephritis by inhibiting transforming growth factor beta mRNA and protein expression. J Autoimmun 8:381-93
Fernandes, G (1995) Effects of calorie restriction and omega-3 fatty acids on autoimmunity and aging. Nutr Rev 53:S72-7;discussion S77-9
Luan, X; Zhao, W; Chandrasekar, B et al. (1995) Calorie restriction modulates lymphocyte subset phenotype and increases apoptosis in MRL/lpr mice. Immunol Lett 47:181-6

Showing the most recent 10 out of 30 publications