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 language | English (US) |
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Pages (from-to) | 747-753 |
Number of pages | 7 |
Journal | Mechanisms of Ageing and Development |
Volume | 125 |
Issue number | 10-11 SPEC. ISS. |
DOIs | |
State | Published - Oct 2004 |
Externally published | Yes |
Keywords
- Aging
- Gene regulation
- Genome instability
- Somatic mutations
ASJC Scopus subject areas
- Aging
- Developmental Biology