Conserved microRNA-networks as regulators of healthy lifespan

Dietary restriction (DR) extends healthy lifespan in diverse species. Age and nutrient-related changes in the abundance of microRNAs (miRNAs) and their processing factors have been linked to organismal longevity. However, the mechanisms by which they modulate lifespan and the tissue-specific role of miRNA-mediated networks in DR-dependent enhancement of lifespan remains largely unexplored. This study shows that two neuronally enriched and highly conserved microRNAs, miR-125 and let-7 mediate the DR response in Drosophila melanogaster. Functional characterization of miR-125 demonstrates its role in neurons while its target chinmo acts both in neurons and the fat body to modulate fat metabolism and longevity. Proteomic analysis revealed that Chinmo exerts its DR effects by regulating the expression of genes involved in fat metabolism. These findings from Dr. Geetanjali Chawla’s group have been published in eLife and in addition to identifying miR-125 as a conserved effector of the DR pathway, this study has opened up the avenue for this small RNA molecule and its downstream effectors to be considered as potential drug candidates for the treatment of late-onset diseases and biomarkers for healthy aging in humans.

In summary, this study has identified miR-125 as an effector of DR pathway. miR-125 is

regulated by dietary signals (DR) and represses chinmo, thus leading to de-repression of genes involved in fat metabolism in peripheral tissues, which in turn result in the extension of lifespan. This functional analysis sets the stage for evaluation of miR-125 and other conserved miRNAs as candidates for developing therapeutics that promote healthy aging and prevent/delay late-onset diseases.

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