Histone acetyltransferases of the CBP/p300 family play the role of transcriptional regulators and are required for a number of biological processes (cell proliferation and differentiation, organism development, regulation of stress response and metabolism). In a study on the fruit fly Drosophila melanogaster, we analyzed for the first time the effect of overexpression and knockdown of the nejire (nej) ortholog gene in various tissues (fat body, intestine, nervous system) on lifespan. The activation of nej had both a positive and a negative effect on this parameter, depending on the driver and the tissue where nej was induced, as well as the sex of the animals. The effect of increasing lifespan (by 6–15%) was found in females with conditional overexpression of nej in the intestine and constitutive overexpression of nej in the nervous system. But in other cases, a shortening of life (up to 44%), or the absence of statistically significant changes were observed. In addition, activation of nej revealed changes in the expression of stress response genes (Sod1, Gadd45, Hsp27, Hsp68, Hif1). At the same time, knockdown of nej in most variants of the experiment caused a pronounced negative effect on the Drosophila lifespan.