Longevity in C. elegans

GEHLE VAUGHN M gehle at ibg.colorado.edu
Fri Dec 17 06:16:20 EST 1993


In article <2em6kmINNkl4 at newsman.csu.murdoch.edu.au>,
Jim Cummins <cummins at possum.murdoch.edu.au> wrote:
>A recent paper in Nature (Kenyon C, Chang J, Gensch E, Rudner A,
>Tabtiang, R: "A  C. elegans mutant that lives twice as long as wild
>type". Nature 366: 461-646: 1993) demonstrated that a single mutation
>in a gene involved in development (daf-2) results in a 2.3  fold
>increase in healthy, fertile lifespan.    Anyone have any ideas on how
>this might function?
>
>Jim Cummins                   
>School of Veterinary Studies
>Murdoch University
>Western Australia 6150  Tel +61-9-360 2668 Fax +61-9-310 4144
>For every complex problem there's a simple solution.  And it's wrong!

In article <2em6kmINNkl4 at newsman.csu.murdoch.edu.au>,
Jim Cummins <cummins at possum.murdoch.edu.au> wrote:
>A recent paper in Nature (Kenyon C, Chang J, Gensch E, Rudner A,
>Tabtiang, R: "A  C. elegans mutant that lives twice as long as wild
>type". Nature 366: 461-646: 1993) demonstrated that a single mutation
>in a gene involved in development (daf-2) results in a 2.3  fold
>increase in healthy, fertile lifespan.    Anyone have any ideas on how
>this might function?

I haven't yet read Cynthia's paper, so I don't know how much of a
description she gives of dauer larvae. Here is a brief and incomplete
description: C elegans has an alternate developmental larval stage called
the dauer. Dauers are very long-lived (70 days or more compared to the
normal adult lifespan of about 15 days), and do not eat, nor reproduce. It
is a method of surviving adverse environmental conditions. Usually dauer
formation is induced by a lack of food, or overcrowding. Once food is
again encountered, the dauer continues its arrested development to become
an adult. It is not known how the dauer is able to survive for so long, but
one interesting point is that dauer larvae have very high levels of SOD
and catalase. 

Daf mutants are defective in one of the genes in the pathway to
dauer formation so that regardless of environmental conditions, larvae
enter the dauer pathway. Some of the daf mutants are long-lived as adults 
(like daf-2), others are not. What is likely happening is that some of 
the dauer mutants turn on parts of the dauer genetic program that never 
get shut down, even after the dauer continues on to adulthood, so that 
the long-lived daf mutants probably are continuing to use as adults the 
metabolic programs that allow long life in the dauer stage. One of those 
programs is probably increased resistance to oxygen radical damage provided
by the elevated SOD and catalase levels. I work in Tom Johnson's lab and 
we are working on another long-lived mutant strain of C elegans, age-1 
mutants, that also have high levels of SOD and catalase, only the levels 
are normal through most of the adult lifespan and only increase in "old 
age". My suspicion is that the daf-2 mutant has elevated SOD and catalase 
throughout its entire adult lifespan, but we have not yet tested this, 
and I don't know if Cynthia Kenyon has either.

Vaughn M. Gehle, Ph. D.
Institute for Behavioral Genetics
University of Colorado
gehle at ibg.colorado.edu





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