COMPARING MUTANTS, SELECTIVE BREEDING, AND TRANSGENICS IN THE DISSECTION OF AGING PROCESSES OF CAENORHABDITIS-ELEGANS

The genetic analysis of aging processes has matured in the last ten ye ars with reports that long-lived strains of both fruit flies and nemat odes have been developed. Several attempts to identify mutants in the fruit fly with increased longevity have failed and the reasons for the se failures are analyzed. A major problem in obligate sexual species, such as the fruit fly is the presence of inbreeding depression that ma kes the analysis of life-history traits in homozygotes very difficult. Nevertheless, several successful genetic analyses of aging in Drosoph ila suggest that with careful design, fruitful analysis of induced mut ants affecting life span is possible. In the nematode Caenorhabditis e legans, mutations in the age-1 gene result in a life extension of some 70%; thus age-1 clearly specifies a process involved in organismic se nescence. This gene maps to chromosome II, well separated from a locus (fer-15) which is responsible for a large fertility deficit in the or iginal stocks. There is no trade-off between either rate of developmen t or fertility versus life span associated with the age-1 mutation. Tr ansgenic analyses confirm that the fertility deficit can be corrected by a wild-type fer-15 transformant (transgene); however, the life span of these transformed stocks is affected by the transgenic array in an unpredictable fashion. The molecular nature of the age-1 gene remains unknown and we continue in our efforts to clone the gene.