Using either the colony formation assay or flow cytometry, it is feasi
ble to measure the frequency of rare mutant lymphocytes or erythrocyte
s in human peripheral blood, Accordingly, we have investigated the mut
ant cell frequencies of the hypoxanthine-guanine phosphoribosyltransfe
rase and T-cell receptor genes in T lymphocytes and of the glycophorin
A gene in erythrocytes of several hundred persons aged 0-96 years. Th
e mutant frequency of every one of these genes increased significantly
with age. A simple accumulation of mutations in hematopoietic stem ce
lls over time may explain the age-dependent increase in the frequency
of glycophorin A mutants. In contrast, a balance between mutant cell g
eneration and loss should be taken into account for the mechanism of t
he increase of T-cell mutations.