age-1(hx546) is a recessive, null mutant of the nematode Caenorhabditis elegans that increases life expectancy and maximum life span more than 70%. Our current working model suggests that this locus coordinately specifies life span, fecundity, and male fertility. This model makes sense from an evolutionary perspective and we propose to test it by isolating and characterizing more alleles, including those which cause obvious deficiencies at age- 1. Specifically we plan to: 1. Isolate new alleles at the age-1 locus using direct screens for longer life using EMS, transposon- tagging, or X-irradiation as mutagens. Alternative screens for detecting age-1 alleles, such as detection of reduced fecundity in heterozygotes opposite age-1(hx546) will be explored. 2. Isolate mutants at other loci involved in the specification of age-related processes. 3. Study the mutants using classical genetic approaches. Mutants identified in parts 1 and 2 will be tested for allelism and mutations genetically mapping using two and three point crosses and deficiency mapping. We will also define epistassis groups using double mutants and explore other genetic procedures, as appropriate. 4. Identify molecular clones of the age-1 locus and other loci involved in the specification of age- related processes using transposon tagging or other approaches in wide use in C. elegans.
