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

Cancers increase during aging in mammals, and an accumulating body of evide nce suggests that mutational events too do likewise. Mutational events are intimately involved in the malignant process. One current view is that muta tor phenotypes are required in malignant cells for a sufficient number of c ritical target genes to be affected. These mutator phenotypes are believed to result from underlying deficiencies in genes necessary to maintain genom ic stability. This review will provide a framework for a discussion of canc er and aging by detailing with a pair of wise approach studies that address the relations between aging, cancer, and mutations. Results from these stu dies will be used to suggest that a mutator phenotype develops in the cells of older individuals in the absence of an underlying genetic deficiency. I nstead, it is proposed that a mixture of chromosomal aberrations, DNA damag e, and chronic exposure to genotoxic forces, including oxidative stress, pr ovide the basis for this age-accelerated mutator phenotype. (C) 2000 Elsevi er Science Ireland Ltd. All rights reserved.