LIFE EXTENSION AND STRESS RESISTANCE IN CAENORHABDITIS-ELEGANS MODULATED BY THE TKR-1 GENE

The nematode Caenorhabditis elegans is widely used to study aging, dev elopment, behavior and other basic metazoan processes [1-3]. The only mutants directly identified on the basis of their extended longevity i n any metazoan have been isolated in C. elegans [4,5]. All life extens ion mutants (Age mutants) previously identified in C, elegans result f rom hypo-morphic or nullo-morphic mutations. We have identified a new class of gerontogene (a gene whose alteration causes life extension) t hat increases life span when overexpressed. The first gene in this cla ss has been designated tyrosine kinase receptor-1 (tkr-1); it encodes a putative receptor tyrosine kinase, Overexpression of tkr-1 in transg enics increases longevity 40-100% (average 65%), confers increased res istance to heat and ultraviolet (UV) irradiation in transgenic nematod es, and does not alter development or fertility, Unlike previously ide ntified gerontogenes, tkr-1 positively modulates stress resistance and longevity. These results further support the positive relationship be tween increased stress resistance and increased longevity seen in all previously studied longevity mutants. This transgenic system is an eff ective means for identifying overexpression gerontogenes.