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Functional genomics of C. elegans aging
Aging is a complex process driven by diverse molecular pathways and biochemical events. Our goal is to first identify genes that are differentially expressed in old versus young animals, and then to dissect apart how changes in these genes lead to functional decline and senescence in old age. We are using the nematode C. elegans as a model system for aging, because it has a rapid lifespan, a small size, a powerful genetic toolkit and many mutants are already known to lengthen lifespan.We have used DNA microarrays to perform a genome-wide screen for genes that change expression in old worms, in the dauer state (an alternative stage with an extremely long lifespan), and in four mutants with altered lifespans. We combined the expression results from these DNA microarray experiments and identified a core set of 233 genes that show consistent changes in expression across different aging experiments.
Having identified age-regulated genes, we propose to study the function of a large number of these genes in parallel, to reveal underlying mechanisms in the process of aging. We are generating GFP reporters for the age-regulated genes in order to use them as biomarkers for age and to reveal which tissues are most susceptible to age-related decline. We will use loss- and gain-of-function experiments to elucidate the function of these genes on aging. Finally, we will elucidate how a GATA transcriptional circuit controls aging, and perform a genome-wide RNAi screen for new aging mutants.
Publications:
Lund et al., Global Profile of Aging in Caenorhabditis elegans. Current Biology, 12, 1566, 2002.