Biography

Instability of the genome has been considered as a possible cause of aging since the late 1940's, when it was discovered that low, daily doses of radiation accelerated symptoms of normal aging in rodents. A connection between damage to the genome and aging was strongly supported by the discovery that heritable defects in genome maintenance are associated with premature aging - as shown in Werner syndrome and Hutchinson Gilford Progeroid syndrome. The defects present in those conditions, and other defects, have been engineered in mice and shown to cause premature aging in these animals as well.

In the past, my laboratory has generated a transgenic mouse model harboring plasmids containing the bacterial lacZ gene. These plasmids can be recovered from genomic DNA and subsequently transferred into E. coli to positively select for colonies representing a mutant lacZ-plasmid. The ratio of colonies of lacZ mutants over lacZ wildtypes is a measure for the mutation frequency in the mouse. In this way we demonstrated that, as predicted, the frequency of mutations increases with age in most tissues and cell types. Our present work is focused on unraveling the mechanisms through which aging-related mutations are induced and obtaining insight as to how increased genomic instability can give rise to some of the most common aging-related phenotypes.

Jan Vijg's Abstract