• Richardson, Arlan G (PI)

Project: Research project

Project Details


One of the most characteristic features of the aging process is
the reduced ability of an organism to maintain homeostasis in
response to stimuli at either the cellular or organ level. Age-
related changes in gene expression, which have been observed in
liver and other tissues, could be an important factor in the age-
related decrease in cell's ability to respond to hormonal signals
and, therefore, to its ability to respond to changes in
environmental and metabolic conditions. Because the regulation
of transcription is the basic site of control for all cells, this type
of cellular change could be important to all cell types. The objective of the research described in this proposal is to
determine if the age-related decline in the expression of
phosphoenolpyruvate carboxykinase (PEPCK) in liver of rats is due
to an alteration in the genetic apparatus of the hepatocyte. The
specific aims of the project and the techniques used for achieving
them are as follows: 1. To establish that the decline in PEPCK expression is due to a
change at the cellular level rather than to an age-related change
in the hormonal status of the animal, the expression of PEPCK
will be studied in cultures of hepatocytes isolated from adult and
old rats. 2. To determine if the ability of the hepatocytes to express
PEPCK in response to a hormonal stimulus becomes ineffective as
an organism ages, the induction of PEPCK expression by cAMP
and/or dexamethasone will be studied in cultured hepatocytes
isolated from adult and old rats. 3. To identify the site (cytoplasmic or nuclear) of the cellular
deficit in PEPCK expression, I will develop and use a
nuclear/cytoplasmic cell-free transcriptional assay prepared from
cultured hepatocytes isolated from adult and old rats. 4. To study the role of chromatin structure in the age-related
decline in PEPCK expression, I will compare the nuclease
hypersensitive sites in the PEPCK gene of the chromatin isolated
from cultured hepatocytes obtained from adult and old rats.
Effective start/end date5/1/884/30/91


  • National Institutes of Health: $16,225.00


  • Medicine(all)


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