Our current emphasis with these techniques is to test candidate genes involved in regulating oxidative stress responses and DNA repair. We are particularly interested in how the post-mitotic muscle and nerve cells of the adult maintain function during aging. Using this method we are identifying additional genes which can extend life span. The second general approach we are taking is to study the regulation of heat shock gene expression as a function of age, in particular the hsp70 and hsp22 genes. We have found that during aging the basal expression of these genes is upregulated at both the transcriptional and posttranscriptional levels, with characteristic temporal and spatial patterns.
Induction appears to be in part due to oxidative stress.
Recent data from other labs demonstrates that a similar pattern of hsp expression is occurring in aging mammals. We are pursuing a detailed analysis of the transcriptional and posttranscriptional regulation of the Drosophila hsp70 and hsp22 genes as a model for this species-general aspect of aging. Chorion gene amplification Chorion gene amplification provides an ideal model for the regulation of higher eukaryotic chromosomal DNA replication origins. Amplification occurs by repeated firing of one or more origins located within each gene cluster. We have cloned and characterized two amplification trans-regulators, k43 and chiffon , and found that they are related to origin regulatory proteins in yeasts, ORC2 and Dbf4 respectively.