The Genetics of Dauer Longevity

Texas Christian University, Fort Worth TX

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Abstract

This proposal falls under research objective 22 (Animal Models of Aging) and is in response to PAR-02-049. With over thirty genes thus far demonstrated to impact its life span, C. elegans has emerged as a leading model system to study the genetic specification of aging. The primary objective of this proposal is to isolate additional life span mutants using a new strategy; namely, genetic screens will be conducted for mutants with altered dauer longevity. These quiescent larvae can survive up to eight times longer than the normal threeweek life span of C. elegans. When favorable environmental conditions are reestablished (usually food presentation), dauer larvae resume development to become adults. For the purposes of this proposal "dauer life span" will be defined as the time that a population of dauers can be incubated in buffer and yet complete development when presented with food. Mutations that confer either shortened and prolonged dauer life span will be subjected to classic genetic analyses (e.g., they will be back-crossed, assigned to a linkage group, mapped and complementation tested when appropriate). These screens should prove successful and yield mutants that further our understanding of the genetics of aging because: i) in general, different selection schemes can allow the recovery of mutations in previously unidentified genes; ii) preliminary data indicate that some C. elegans life span mutants (e.g.,age-I, mev-1, clk- 1) have altered dauer life spans; iii) mutations in a number of different genes (e.g., the myriad that control catabolism, anabolism, oxidative stress resistance) should impact dauer life span; and iv) in contrast to the genetics of dauer larvae formation, virtually nothing is known about the factors controlling dauer longevity. Therefore, it is anticipated that subsequent analyses of these mutants will provide insights into the various factors that determine dauer life span. The second main focus of the grant wilt be to comprehensively determine the dauer longevity for a set of extant "aging" mutants (e.g., age-l, daf-2, clk-1, mev-1) in order to determine the extent to which the genetics of adult life span and dauer life span overlap. Finally, the effects of environmental parameters such as oxidative stress and temperature will be tested for their impact on the dauer longevity. Collectively these experiments should provide a foundational basis for future, more systematic examinations of dauer longevity.