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Aging and Genome Maintenance
Author(s) -
VIJG JAN,
BUSUTTIL RITA A.,
BAHAR RUMANA,
DOLLÉ MARTIJN E.T.
Publication year - 2005
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1323.007
Subject(s) - genome instability , biology , somatic cell , gene , mutation , genetically modified mouse , genetics , transgene , genome , neoplastic transformation , mutation rate , microbiology and biotechnology , dna , carcinogenesis , dna damage
Genomic instability in somatic cells has been implicated as a major stochastic mechanism of aging. Using a transgenic mouse model with chromosomally integrated lacZ mutational target genes, we found mutations 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 degeneration, 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.