• Richardson, Arlan G (PI)

Project: Research project

Project Details


DESCRIPTION Dietary restriction, i.e. the
restriction of total calories, is the only effective method for increasing
the maximum survival of mammals, and it is believed that the increase in
survival is due to an alteration in the aging process(es). Therefore,
dietary restriction is a powerful tool for studying the biolobical
mechanism underlying the aging process and the impact of nutrition on the
aging process. Several years ago, the applicant proposed that dietary
restriction was acting at the level of gene expresssion. During the past
three years, the applicant's laboratory has shown that dietary restriction
alters the age-related change in the levels of a variety of mRNA species in
several tissues from rat, and that the alteration in mRNA levels is
paralelled by an alteration in nuclear transcription. Thus, he has shown
that dietary restriction does indeed alter gene expression and that this
alteration occurs primarily at the level of transcription. The purpose of
the research described in this proposal is to elucidate the molecular
mechanism through which dietary restriction alters the transcription of
genes. Specifically the applicant will test the following hypothesis: the
changes in transcription that arise from dietary restriction are due to
changes in the levels/activities of specific transcription factors that
regulate the transcription of specific genes. This hypothesis will be
tested by studying the expression of the gene for a heat shock protein, hsp
70, in hepatocytes or lymphocytes isolated from male Fisher F344 rats fed
ad libitum or a calorie-restricted diet (60% of diet consumed by rats fed
ad libitum). The specific objectives of the research described in this
proposal are as follows: (1) To characterize the effect of aging and
dietary restriction on the induction of hsp70 expression (synthesis, mRNA
levels, and transcription) by heat shock and a heavy metal, and to
characterize the expression of hsp70 by individual cells from young and old
rats fed ad libitum and the restricted-diet by in situ hybridization; (2)
to characterize the effect of aging and dietary restriction on the
initiation of hsp70 transcription by the in vitro and in vivo transcription
of hsp70 promoter-reporter templates; and (3) to characterize the effect of
aging and dietary restriction on transcription factors that regulate hsp70
expression. The activation (DNA binding) and expression (i.e., protein and
mRNA levels) of heat shock transcription factor as well as CAAT-box
transcription factor and Sp1 will be determined in young and old rats on
the two diets.
Effective start/end date7/1/793/31/99


  • National Institutes of Health: $204,616.00
  • National Institutes of Health: $199,283.00


  • Medicine(all)


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