In his global quest for the fountain of youth, I’m not sure Ponce de Leon ever thought of the humble fruit fly (Drosophila melanogaster) beating him to the punch. Yet, new data from investigators at the Engelhardt Institute of Molecular Biology, within the Russian Academy of Sciences could bring us much closer to understanding the underlying molecular mechanism of biological longevity. Findings from this interesting new study were published recently in Scientific Reports through an article titled “Transcriptome Analysis of Long-lived Drosophila melanogaster E(z) Mutants Sheds Light on the Molecular Mechanisms of Longevity.”

Using genome-wide transcriptome analysis, the team noted that lifespan extension and stress resistance in Drosophila carrying the E(z) histone methyltransferase heterozygous mutation—E(z) mutation for short—were correlated with changes in the expression levels of 239 genes. The expression levels of some of the genes were doubled in flies with the E(z) mutation.

“We demonstrated that lifespan extension, increase of resistance to hyperthermia, oxidative stress and endoplasmic reticulum stress, and fecundity enhancement in E(z) heterozygous mutants are accompanied by changes in the expression level of 239 genes (p < 0.05),” the authors wrote. “Our results demonstrated sex-specific effects of E(z) mutation on gene expression, which, however, did not lead to differences in lifespan extension in both sexes. We observed that a mutation in an E(z) gene leads to perturbations in gene expression, most of which participate in metabolism, such as carbohydrate metabolism, lipid metabolism, drug metabolism, and nucleotide metabolism.”

According to the results of the study, the mutant flies had a 22–23% lifespan extension compared to the control group. In addition, these flies were more resistant to hyperthermia, oxidative stress, and endoplasmic reticulum stress, which can disrupt processes designed to help cells stay healthy. The mutant flies were also more fertile, the researchers added.

“We demonstrated that the E(z) mutation affect a plethora of poorly described Drosophila genes,” the authors noted. “The functions of these genes in lifespan determination are not understood and may not be associated with aging and longevity.

E(z) genes appear connected with gene expression that affects metabolism, such as carbohydrate metabolism, lipid metabolism, drug metabolism, and nucleotide metabolism. The expressions related to aging were involved in pathways related to the immune response, cell cycle, and ribosome biogenesis.

“The findings of the conducted research may be a step toward investigating whether the E(z) mutation could play a role in human longevity and have implications for understanding the role of global depression of chromatin in aging,” remarked lead study investigator Alexey Moskalev, PhD, head of the laboratory of geroprotective and radioprotective technologies.

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