Mutation accumulation in mice of extended life span

Project: Research project

Project Details


DESCRIPTION: (Verbatim from the application) Mutation accumulation in mice of
extended life span.
Genomic instability has been implicated as a major cause of both cancer and
aging. Using a transgenic mouse model with chromosomally integrated lacZ
mutational target genes, we have recently demonstrated that mutations
accumulate with age in an organ-specific manner. That is, both the rate of
accumulation and the types of mutations that accumulate were found to differ
from organ to organ. The hypothesis central to the proposed project is that the
rate of mutation accumulation and the types of mutations that accumulate in
various organs and tissues is intricately related to basic mechanisms of aging,
possibly through general metabolism. To test this hypothesis and obtain more
insight into the relevant pathways involved, we propose to study mutation
accumulation in the lacZ mice under caloric restriction and in lacZ hybrids
with the Ames dwarf mice. In both CR and the dwarf mouse, life span is extended
and tumor formation reduced, possibly due to related mechanisms, in which
reduced oxidative stress and/or reduced cell division could play a role. These
same mechanisms may also retard mutation accumulation and/or influence the
mutational spectra. The results of these studies could lead to new strategies
to interfere with basal mutation rates to prevent and/or retard cancer and
other deteriorative aspects of aging
Effective start/end date7/1/016/30/11


  • Genetics
  • Molecular Biology
  • Medicine(all)
  • Cancer Research


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