Aging-Specific Gene Expression in Drosophila

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Heat shock proteins (hsps) are induced in all species in response to heat and other stresses. hsps appear to be involved in prevention and repair of protein damage and can confer increased heat and oxidative stress resistance to many cell types. Drosophila hsp70 and hsp22 are induced in a characteristic, tissue-specific pattern during aging. This aging associated upregulation involves both transcriptional and posttranscriptional mechanisms, and appears to be in part a response to oxidative damage. hsp22 exhibits the largest aging- related upregulation known for any eukaryotic gene (greater than 150-fold). The expression of homologous hsps is upregulated in humans during normal aging and in numerous pathophysiological and aging-related disease states. In both Drosophila and mammals the chronic upregulation of hsp genes during aging is associated with a reduced ability of the organism to hyper-induce the genes and survive an acute heat stress. We hypothesize that altered hsp gene expression is a species-general biomarker of aging and life span, and is related to the species-general phenomena of decreased protein synthesis and turnover. We propose to study the aging-related transcriptional and posttranscriptional regulation of Drosophila hsp70 and hsp22 in detail. The research involves genetic and transgenic manipulation of hsp gene expression and aging in Drosophila. The experiments will test several specific hypotheses relating aging and hsp gene expression.