• Fernandes, Gabriel (PI)

Project: Research project

Project Details


Our long-term goal is to elucidate the mechanisms whereby moderate food
restriction (FR) increases immune function, delays the appearance of age-
associated disease processes and significantly prolongs life span. We
observed higher lymphocyte proliferative responses, higher anti-
inflammatory lymphokine production, changes in long-chain fatty acids in
lymphocyte membranes and age-related changes in gene expression in aging
food-restricted rats. Our recent studies revealed that FR delays the
rise of memory T-cells and also the loss of CD4+ T-cell proliferative
response to superantigens (staphylococcal enterotoxin-B) indicting that
changes in rat Vbeta+ subsets may occur with age. We propose that age-
related changes in both T-cell subsets and membrane integrity may
modulate various cellular functions and transmembrane signaling
apparatus. The aim of this proposal is to test the hypothesis that FR
modifies T-cell functions, including virgin and memory T-cell subset
functions, and suppresses the rise in pro-inflammatory cytokines released
by T-cells and macrophages (Mphis). Our proposal will address the
following: 1) The mechanism(s) underlying T-cell defects with age:
analyze the functional changes in purified T-cell subsets obtained from
spleens of both ad libitum and food-restricted rats at 6, 18 and 36
months of age, as well as the frequency and functional loss of
alloreactive CD4+ and CD8+ T-cell subsets, their lymphokine production
(IL-2, gamma-IFN, IL-4) and also mRNA expression. 2) The characteristics
of age-associated functional and quantitative changes in virgin
(CD45RChigh) and memory (CD45RClow) T-cells within CD4+ and CD8+ T-cell
subsets: measure pro- and anti-inflammatory lymphokine production, and
the proliferative response to various stimulatory agents including
bacterial superantigens and recall antigens. 3) Determine if age-
associated proliferative responses in T-cell subsets correlate with
increased release of pro-inflammatory cytokines by Mphis: measure PGE2,
IL-1, IL-6 and TNF-alpha by activating in vitro, both resident and
elicited peritoneal Mphis. Finally, the correlation between T-cell
immunological dysfunction and changes in membrane phospholipid
composition and fluidity with age and diet will be determined. to
achieve the above specific aims, we will use female Fischer-344 x Brown
Norway F1 rats as these rats live relatively long and are free of common
diseases. these studies should enable us to understand the fundamental
mechanisms involved in maintaining an active immune system during aging
through reduced caloric intake and may thus provide valuable information
on maintaining a healthy life span for our rapidly growing aging
Effective start/end date9/15/932/28/99


  • National Institutes of Health: $174,995.00
  • National Institutes of Health: $99,777.00
  • National Institutes of Health: $162,191.00


  • Medicine(all)


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