EFFECT OF AGING ON GENE EXPRESSION

  • Richardson, Arlan G (PI)

Project: Research project

Project Details

Description

Most of the research conducted during the past twenty years has shown that
a general decline in translation and transcription occurs with increasing
age; however, essentially no information is currently available on the
effect of age on the expression of specific genes. Although changes in
gene expression are essential in mitogenesis, no information is now
available on the role that gene expression might play in the
well-documented, age-related decline in mitogenesis. Preliminary
experiments conducted in the laboratories of the two Principal
Investigators show that an age-related decline in total protein synthesis
occurs in cultured lymphocytes. This decline is correlated with a decline
in mitogenesis and interleukin-2 (IL2) production. The following hypothesis will be tested in the research described in this
proposal: a decline in the expression of the gene for IL 2 by IL
2-producing T-cells is responsible for the age-related decline in IL 2
production by stimulated spleen lymphocytes. The genetic expression of IL
2 by 6- to 32-month-old Fischer F344 rats will be studied using spleen
lymphocytes stimulated with concanavalin A. The absolute rates of IL 2
synthesis by limphocytes will be determined by measuring the rates of
[3H]-valine incorporation into products that are immunoprecipitated by a
monoclonal antibody to IL 2 and by measuring the specific activity of the
valine precursor pool. The relative amounts of IL 2 mRNA in RNA isolated
from lymphocytes will be quantified by dot hybridization with a cDNA probe
to IL 2 mRNA. In addition, experiments will be conducted to establish that
the age-related decline in IL 2 expression does not occur because of
age-related changes in IL 1 production by macrophages or the number of IL
2-producing T-cells. Because IL 2 plays a critical role in mitogenesis and
because the addition of exogenous IL 2 to lymphocyte cultures appears to
reverse the age-related decline in mitogenesis, a knowledge of how aging
affects the expression of IL 2 will be very important in our understanding
of the age-related decline in the immune system. The long range objective
of our research is to elucidate the role that gene expression plays in the
aging process.
StatusFinished
Effective start/end date12/1/8411/30/87

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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