Homologs of the yeast longevity gene LAG1 in Caenorhabditis elegans and human

LAG1 is a longevity gene, the first such gene to be identified and cloned f rom the yeast Saccharomyces cerevisiae. A close homolog of this gene, which we call LAC1, has been found in the yeast genome. We have cloned the human homolog of LAG1 with the ultimate,ooal of examining its possible function in human aging. In the process, we have also cloned a homolog from the nema tode worm Caenorhabditis elegans. Both of these homologs, LAG1Hs and LAG1Ce -1 functionally complemented the lethality of a lag1 Delta lac1 Delta doubl e deletion, despite low overall sequence similarity to the yeast proteins. The proteins shared a short sequence, the Lag1 motif, and a similar transme mbrane domain profile. Another, more distant human homolog, TRAM, which lac ks this motif, did not complement. LAG1Hs also restored the life span of th e double deletion, demonstrating that it functions in establishing the long evity phenotype in yeast. LAG1Hs mapped to 19p12, and it was expressed in o nly three tissues: brain, skeletal muscle, and testis. This gene possesses a trinucleotide (CTG) repeat within exon 1. This and its expression profile raise the possibility that it may be involved in neurodegenerative disease . This possibility suggests at least one way in which LAG1Hs might be invol ved in human aging.