Senior Scholar Award in Aging
James F. Nelson, Ph.D.
University of Texas Health Science Center - San Antonio

Rapid Screening for Longevity Mutants in Mice

Mutational screens in C. elegans and D. melanogaster demonstrate that single gene mutations can extend life span. The phenotypes associated with these mutations include reduced insulin and/or insulin-like growth factor signaling and increased resistance to oxidative and other life-threatening stressors. Mammalian models of extended life span also show altered insulin/insulin-like growth factor signaling and increased stress resistance. In addition, they exhibit reduced body mass. We therefore hypothesize that genetic screening of young mice for mutants exhibiting these traits will select for genotypes with extended life span. We will utilize the mutant mice being generated by ENU mutagenesis programs throughout the world. The working hypothesis is that genetic screens of young mice for mutants exhibiting extremes of these traits will enable the rapid selection of candidate genotypes with extended (and shortened) life span. This experimental design uses a growing pool of genetic variants in which the mutated genes are ultimately identifiable. It directly tests three important hypotheses about mammalian aging, and can ultimately lead to the identification of genes that influence the aging process.

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