Worm Breeder's Gazette 12(5): 94 (February 1, 1993)

These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.

A Mutation Which Doubles C. elegans Life Span (Imagine Being 140)

Adam Rudner, Ramon Tabtiang, Cynthia Kenyon

UCSF, CA. 94143

We have discovered that the strain CB1370 has a mean life span twice that of N2 when raised at 20°. The mean life span of CB1370 is 45 days whereas the mean life span of N2 is 21 days. The increase in life span of this strain is striking. After 31 days, when all the N2 worms have died, 84% of the CB1370 worms are still alive and moving well on their plates.

CB1370 contains the mutation daf-2 ( e1370 ). daf-2 ( e1370 Jis a temperature-sensitive dauer-constitutive mutation. Worms hatched and raised at 25° enter dauer and remain as dauer larvae until shifted to the non-permissive temperature of 20°. Dauer larvae are morphologically different from non-dauer animals and have an increased life span. At 20° CB1370 exhibits increased longevity but not other dauer phenotypes. It eats and produces progeny, and it looks much like a normal non-dauer animal. We have also observed a similar increase in life span when CB1370 worms are hatched at 20° and shifted to 25° as L4 sor early adults. This increase in life span is not as dramatic, however, because a large number of CB1370 worms become bags at 25°.

It has generally been assumed the dauer lives longer simply because it is relatively metabolically inert. However, this result suggests that perhaps the longevity of the dauer is not simply due to its being in a state of suspended animation. Instead, there may be a longevity program latent in the non-dauer worm that can, if activated, prolong its life substantially. The longevity program is normally activated along with other aspects of dauer morphogenesis, but the increased lifespan of daf-2 (1370)mutants suggests that it can function independently.

Although the mutation in daf-2 is the most likely reason for increased longevity in CB1370 ,there is the possibility that CB1370 contains a second mutation, in an "aging" gene and that daf-2 ( e1370 )has no longevity phenotype. In order to differentiate between these two possibilities we are currently testing other daf-2 alleles for increased life span. Preliminary findings suggest that daf-2 ( sa193 ),kindly sent to us by Jim Thomas, also lives longer than the wild-type.

We conclude that daf-12 wild-type activity is dispensible for the heterochronic expression of the L1 -specificantigen caused by the dauer-constitutive mutations we tested. In