miR-125-chinmo pathway regulates dietary restriction-dependent enhancement of lifespan in Drosophila

Author:

Pandey Manish1,Bansal Sakshi1,Bar Sudipta2,Yadav Amit Kumar3ORCID,Sokol Nicholas S4,Tennessen Jason M4ORCID,Kapahi Pankaj2,Chawla Geetanjali1ORCID

Affiliation:

1. RNA Biology Laboratory, Regional Centre for Biotechnology, Faridabad, India

2. Buck Institute for Research on Aging, Novato, United States

3. Translational Health Science and Technology Institute, Faridabad, India

4. Department of Biology, Indiana University, Bloomington, United States

Abstract

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.

Funder

Wellcome-Trust DBT India Alliance

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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