4-4-Phenylbutyrate (PB), present in plants and royal jelly (RJ), plays a vital part in honeybee longevity. Phenylacetylglutaminate (PG) is a metabolite of PB. The aim of this research was to study changes in gene expression in honeybee workers fed with PB+PG-supplemented diet (in 50% sucrose syrup) by gene array and pathway analysis of their brains, and to perform cage longevity studies. The control group received sucrose syrup only. The statistical analysis of microarray results was performed with Genespring and LimmaGUL. Functionally related genes were identified with the help of Gene Ontology in Gostat. A detailed pathway analysis was conducted by importing annotated gene lists to the PathwayArchitect. The most significant results were noted in chromatin remodeling, the TCA cycle, glutathione system (up-regulation), and Notch signaling (down-regulation), which may contribute to increased longevity. These results suggest that PB and PG increase the expression of genes that play an important part in development and life extension. The study of the longevity of caged honeybees consisted in feeding larvae and worker bees with PB+PG-supplemented diet, and comparing them with non-supplemented controls. In three longevity experiments, the bees that were given PB+PG at the larval stage lived longer. This points to a long-term epigenetic effect, which has not been observed in earlier studies.
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