DIET AND AUTOIMMUNITY AND AGING

  • Fernandes, Gabriel (PI)

Project: Research project

Project Details

Description

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.
StatusFinished
Effective start/end date9/15/816/30/96

Funding

  • National Institutes of Health: $168,165.00
  • National Institutes of Health: $198,248.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $17,400.00

ASJC

  • Medicine(all)

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