Current approaches to somatic mutation testing in aging research

Abstract

The somatic mutation theory of aging, put forth over 30 years ago, was originally based on the observation that exposure to ionizing radiation could induce an “aged” phenotype and reduce lifespans in experimental animals. According to this theory, the age-related accumulation of genetic mutations could lead to an incremental loss of function, and eventually to the complex phenotypes characteristic of advancing age. Historically, methods used to measure and characterize mutational events at the somatic level have been limited to the use of easily clonable cell types in conjunction with an assay to detect loss of expression of a particular gene or allele. Reviewed here are some of the commonly used techniques for the quantitation and characterization of somatic mutations both in vitro and in vivo. Particular attention is paid to recent advances in genetic technology which have resulted in the availability of more reliable techniques including transgenic models for both the determination of mutation frequencies and the characterization of mutational spectra in vivo. These models clearly represent valuable tools for studying the relationships between mutagenesis, genetic instability and basic mechanisms of aging.