Genetic and Environmental Manipulation of Aging in Caenorhabditis elegans

Abstract

For aging studies, the small soil nematode Caenorhabditis elegans offers the potential advantages of a short life span and ease of culture in large numbers, coupled with a reproductive mode (self-fertilizing hermaphroditism) which facilitates mutant isolation and thus might make possible a genetic dissection of the aging process ^1,2. To use these advantages productively and in a generalizable way, we decided some time ago, in collaboration with our colleague Lewis A Jacobson, that three additional conditions would have to be met. First, it would have to be established how general C. elegans aging is, i.e. to what extent it exhibits properties observed during aging in other organisms, especially mammals. Second, aging in C. elegans would have to be operationally defined, in a way which would permit it to be measured during manipulations aimed at altering the aging process; our view, in contrast to that of others working on many different systems, was that mere measurement of mortality (survival) statistics was not an adequate operational definition for this purpose. Third, it would have to be established whether useful genetic aging variants could be obtained in C. elegans; useful variants in this sense meant to us variants with only single-gene alterations (so that the basis of the aging effect would have some reasonable prospect of becoming understood) and in which related effects were demonstrable on more than just one of the processes which change with age (so that the genetically affected step would have a reasonable prospect of being central, rather than peripheral, to aging).