Deleterious mutations, that affect either function or expression of genes, also negatively influence flux through biochemical pathways and networks they are associated with. Such changes reduce fitness and organisms are therefore selected to buffer any such effects. Not surprisingly, gene expression level is therefore not directly related to gene dose in Drosophila melanogaster. Instead, many studies have shown that gene expression in small regions of the genome that artificially have been made haploid or triploid is biased towards the expression level in diploids. This effect is probably partly explained by feedback regulation in gene networks, which is an inherent property of biochemical pathways. However, since it has been shown than many genes show condition dependent expression, this mechanism is presumably also used to allocate energy into maintaining homeostasis in disturbed biochemical pathways. Energy is then channelled away from other activities, which hence could reduce the amount of resources available for somatic maintenance and result in faster accumulation of damage and ageing. This scenario could potentially also result in a downward spiral, where less resources available for buffering causes even more aberrant expression and costs, speeding up the rate of ageing even further. Deletions provide a unique opportunity to test this idea. If an individual’s capacity to buffer mis-expressed genes is reduced with age, expression of genes located in heterozygous deletions should reduce with age. These genes should then cause progressively more harm to the individual. This project tests this possible ageing mechanism. We have introgressed deletions into our fly population over 10 generations and produced daughters heterozygous for the deletions and matched control wild type daughters from the same crosses. These flies have then ben kept together and flies have been culled from both genotypes, both at a young and an old age. RNA has subsequently been extracted from these flies and this RNA has been sequenced. The main questions that will be addressed are (i) if expression levels of genes located in the deletions gradually decline with age and (ii) if genes in the biochemical pathways the deleted genes are associated with show more mis-expression with age than genes in other pathways.