The somatic mutation theory of aging, put forth over 30 years ago, was
originally based on the observation that exposure to ionizing radiati
on could induce an ''aged'' phenotype and reduce lifespans in experime
ntal animals. According to this theory, the age-related accumulation o
f 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 eve
nts at the somatic level have been limited to the use of easily clonab
le cell types in conjunction with an assay to detect loss of expressio
n of a particular gene or allele, Reviewed here are some of the common
ly used techniques for the quantitation and characterization of somati
c mutations both in vitro and in vivo. Particular attention is paid to
recent advances in genetic technology which have resulted in the avai
lability of more reliable techniques including transgenic models for b
oth the determination of mutation frequencies and the characterization
of mutational spectra in vivo, These models clearly represent valuabl
e tools for studying the relationships between mutagenesis, genetic in
stability and basic mechanisms of aging.