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. We show 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 FATP, CG2017, CG9577, CG17554, CG5009, CG8778, CG9527, and FASN1. Our findings identify miR-125 as a conserved effector of the DR pathway and open 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.
All data generated or analyzed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1, 2, 3, 4, 5, 6, 7, 8.Proteomics analysis data done in Figure 7 is also provided in Supplementary files 3 and 4 (Upregulated and downregulated processes).
- Geetanjali Chawla
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Dario Riccardo Valenzano, Max Planck Institute for Biology of Ageing, Germany
- Received: September 1, 2020
- Accepted: June 7, 2021
- Accepted Manuscript published: June 8, 2021 (version 1)
© 2021, Pandey et al.
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