ABSTRACT
This chapter examines critically the evidence for genomic instability in postmitotic mammalian cells during their life span and the effects of aging on the stability of mitochondrial genomes. The presence of abnormal chromosomes in dividing cells is a classical cytological index of genomic instability. The fraction of liver cells containing radiation-induced chromosomal aberrations decreases with time from some initial level toward the spontaneous level, but never appears to reach the uninduced levels for age-matched controls. Aberrant chromosomes include dicentric chromosomes, acentric chromosomes, centric ring fusions, chromosomal deletions, inversions, breakage and translocations, and chromatid gaps or breaks. Variable number of tandem repeats, or minisatellite loci, is unstable genetic elements. As part of the aging process, random loss of methyl groups in DNA may lead to aberrant epigenetic changes in gene expression and perhaps affect chromosomal stability. DNA damaging agents may participate in epigenetic mechanisms that alter chromatin structure, gene expression, and DNA metabolism, for example, recombination.
