Diverse Caenorhabditis elegans genes that are unregulated in dauer larvae also show elevated transcript levels in long-lived, aged, or starved adults

Under adverse conditions, the nematode Caenorhabditis elegans undergoes rev ersible developmental arrest as dauer larvae, an alternative third larval s tage adapted for dispersal and long-term survival. Following such arrest, w hich may exceed three times their usual Life-span, worms resume development to form reproductive adults of normal subsequent longevity. Mutations of g enes in the dauer-formation (daf) pathway can extend life-span two- to four fold, even in adults that mature without diapause. To identify transcript-l evel changes that might contribute to extended survival, we prepared a subt ractive cDNA library of messages more abundant in dauer than in non-dauer ( L3) larvae. Six genes were confirmed as three- to ninefold upregulated in d auer larvae, after correction for mRNA load: genes encoding poly(A)-binding protein (PABP), heat-shock proteins hsp70 and hsp90, and three novel genes of uncertain function. The novel genes encode a partial homologue of human activating signal cointegrator 1 (ASC-1), a GTP-binding homologue of a rib osomal protein, and an SH3-domain protein. Transcript levels for all except hsp70 increased during aging in two C. elegans strains, whereas the three novel genes (and possibly PABP) were also induced to varying degrees by sta rvation of adults. All six genes are expressed at higher levels in young ad ults of long-lived daf mutant strains than in normal-longevity controls, su ggesting that increased expression of these genes may play a protective fun ction, thus favoring survival in diverse contexts. (C) 2000 Academic Press.