Tissue-specific time courses of spontaneous mutation frequency and deviations in mutation pattern are observed in middle to late adulthood in Big Blue mice.

摘要: To better define the time course of spontaneous mutation frequency in middle to late adulthood mouse, measurements were made at 10, 14, 17, 23, 25, and 30 months age samples adipose tissue, liver, cerebellum (90% neurons), male germline (95% germ cells). A total 46 million plaque-forming units (pfus) screened six points 1,450 circular blue plaques harvested sequenced. These data improve resolution confirm previously observed occurrence least two tissue-specific profiles (elevation with tissue constancy neurons cells), a low germline, pattern unchanged within tissue. findings appear extend very old (30 months). Additional include interanimal variation is larger tissues liver compared cells, subtle but significant differences among tissues, consistent minor effect metabolism. The presumptive unaltered balance DNA damage repair has evolutionary consequences. It particular interest given controversy over whether or not increasing paternal underlies reports associating older males higher incidence some types genetic disease. most detailed available date regarding individual help constrain hypotheses role mutational mechanisms aging.