Spontaneous mutations in ageing human cells: studies using a Herpesvirus probe

Several fundamental theories of ageing postulate that spontaneous mutations increase in somatic cells as they age. This has not until recently been directly tested in mammalian cells, because of the problem of estimating mutation rate in declining cell populations. One possible approach is to infect cells with lytic virus and measure the mutation frequency in virus made by the cellular machinery. Three temperature-sensitive mutants of Herpesvirus were used to infect human fibroblasts in vitro. The reversion frequency was examined in virus harvested from young and old cells. It was found that with tsE there was a hundredfold increase in reversion rate in old compared to young cells, with tsD the rates were roughly similar and with tsG a fortyfold decrease in old cells. These differences are not due to differential rates of virus production. It is proposed that errors in specific functions in old cells influence the spontaneous mutation rate of the three viral mutants in opposite directions. It is pointed out that certain unknown factors limit the usefulness of viral probes in ageing research and cast doubt on previous work of this type.