Genetic and Molecular Basis of Longevity

Massachusetts General Hospital, Boston MA

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Abstract

From a combination of genetic analyses and RNAi screening, we have discovered hundreds of gene inactivations and mutations that regulate C. elegans lifespan. We propose to GFP tag these genes to discern their molecular identity as well as to delineate from their expression pattern which cells mediate the regulation of aging. We will determine the cellular focus of gene activity for aging and whether any of the genes encode proteins that mediate the signaling cellular stress in those cells. C. elegans is amenable to large scale genetic and functional genomic screens which is not feasible in mice. Our worm genomics highlights scores of human genes which are homologues of the worm genes we have identified. In some cases, the genes encode proteins that are attractive for the development of drugs. Therefore, identification of aging pathway genes in C. elegans provides targets for intervention of human aging.