Somatic cell mutations: can they provide a link between aging and cancer?

Cancers increase during aging in mammals, and an accumulating body of evidence suggests that mutational events too do likewise. Mutational events are intimately involved in the malignant process. One current view is that mutator phenotypes are required in malignant cells for a sufficient number of critical target genes to be affected. These mutator phenotypes are believed to result from underlying deficiencies in genes necessary to maintain genomic stability. This review will provide a framework for a discussion of cancer and aging by detailing with a pair of wise approach studies that address the relations between aging, cancer, and mutations. Results from these studies will be used to suggest that a mutator phenotype develops in the cells of older individuals in the absence of an underlying genetic deficiency. Instead, it is proposed that a mixture of chromosomal aberrations, DNA damage, and chronic exposure to genotoxic forces, including oxidative stress, provide the basis for this age-accelerated mutator phenotype.