Life extension and stress resistance in Caenorhabditis elegans modulated by the tkr-1 gene

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