Project: Research project

Project Details


DESCRIPTION (Adapted from the Applicant's Abstract): Glutathione (GSH) is a
major antioxidant present in high concentrations in nearly all living cells,
with numerous critical functions in cellular homeostasis and defense. The
investigator's previous results and those of others suggest that GSH
depletion is a general phenomenon of aging tissues and organisms. They
hypothesize that the loss of GSH is caused by an impairment in its
biosynthesis and represents a key factor in the biological aging process,
based upon its essential roles. While considerable data have been
accumulated to support the important role for GSH in aging, little
information is available regarding the mechanisms responsible for its
depletion during aging.

The overall goals of the present research proposal are to determine the
cause of the GSH deficiency in the aging mouse and to elucidate the
mechanisms by which caloric restriction (CR) increases GSH and prevents the
aging-deficiency. To this end, they will determine the effects of aging and
CR on the metabolism of Met, Cys and GSH in the C57BL/6 mouse model. In
addition, they will also examine the effects of specific enhancement and
depletion of GSH on longevity, using lifelong feeding with GSH monoethyl
ester and buthionine sulfoximine, respectively.

A systematic and multi-level approach will be used to assess metabolism.
The specific activities of the enzymes involved in GSH, Cys and Met
metabolism will be determined along with the levels of specific intermediate
metabolites in different tissues. GSH turnover will be assessed on whole
animals by injection of radiolabeled precursors. Animals of 4 age groups
will be analyzed in order to assess growth and developmental changes as well
as aging-specific changes.

The results of these studies will provide new information on the biochemical
mechanisms of the aging process, which will be important in the development
of strategies to enhance health and longevity.
Effective start/end date2/6/971/31/01


  • National Institute on Aging
  • National Institute on Aging
  • National Institute on Aging


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