Impact of genome instability on transcription regulation of aging and senescence

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Genomic instability has been implicated as a major stochastic mechanism of aging. Using a transgenic mouse model with chromosomally integrated lacZ mutational target genes, mutations were found to accumulate with age at an organ- and tissue-specific rate. Also, the spectrum of age-accumulated mutations was found to differ greatly from organ-to-organ; while initially similar, mutation spectra of different tissues diverged significantly over the lifetime. To explain how genomic instability, which is inherently stochastic, can be a causal factor in aging, it is proposed that randomly induced mutations may adversely affect normal patterns of gene regulation, resulting in a mosaic of cells at various stages on a trajectory of functional decline, eventually resulting in cell death or neoplastic transformation. To directly address this question, we demonstrate that it is now possible to analyze single cells, isolated from old and young tissues, for specific alterations in gene expression.

Original languageEnglish (US)
Pages (from-to)747-753
Number of pages7
JournalMechanisms of Ageing and Development
Volume125
Issue number10-11 SPEC. ISS.
DOIs
StatePublished - Oct 1 2004
Externally publishedYes

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Keywords

  • Aging
  • Gene regulation
  • Genome instability
  • Somatic mutations

ASJC Scopus subject areas

  • Aging
  • Developmental Biology

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