miR-125-chinmo pathway regulates dietary restriction-dependent enhancement of lifespan in Drosophila
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...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-06-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/62621 |
| _version_ | 1811201412315480064 |
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| author | Manish Pandey Sakshi Bansal Sudipta Bar Amit Kumar Yadav Nicholas S Sokol Jason M Tennessen Pankaj Kapahi Geetanjali Chawla |
| author_facet | Manish Pandey Sakshi Bansal Sudipta Bar Amit Kumar Yadav Nicholas S Sokol Jason M Tennessen Pankaj Kapahi Geetanjali Chawla |
| author_sort | Manish Pandey |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T02:21:19Z |
| format | Article |
| id | doaj.art-89e6fb71bceb40c682285f5113659ac7 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:21:19Z |
| publishDate | 2021-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-89e6fb71bceb40c682285f5113659ac72022-12-22T03:52:07ZengeLife Sciences Publications LtdeLife2050-084X2021-06-011010.7554/eLife.62621miR-125-chinmo pathway regulates dietary restriction-dependent enhancement of lifespan in DrosophilaManish Pandey0Sakshi Bansal1Sudipta Bar2Amit Kumar Yadav3https://orcid.org/0000-0002-9445-8156Nicholas S Sokol4Jason M Tennessen5https://orcid.org/0000-0002-3527-5683Pankaj Kapahi6Geetanjali Chawla7https://orcid.org/0000-0003-0354-3716RNA Biology Laboratory, Regional Centre for Biotechnology, Faridabad, IndiaRNA Biology Laboratory, Regional Centre for Biotechnology, Faridabad, IndiaBuck Institute for Research on Aging, Novato, United StatesTranslational Health Science and Technology Institute, Faridabad, IndiaDepartment of Biology, Indiana University, Bloomington, United StatesDepartment of Biology, Indiana University, Bloomington, United StatesBuck Institute for Research on Aging, Novato, United StatesRNA Biology Laboratory, Regional Centre for Biotechnology, Faridabad, IndiaDietary 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.https://elifesciences.org/articles/62621microRNAsdietary restrictionagingmiR-125fat metabolism |
| spellingShingle | Manish Pandey Sakshi Bansal Sudipta Bar Amit Kumar Yadav Nicholas S Sokol Jason M Tennessen Pankaj Kapahi Geetanjali Chawla miR-125-chinmo pathway regulates dietary restriction-dependent enhancement of lifespan in Drosophila eLife microRNAs dietary restriction aging miR-125 fat metabolism |
| title | miR-125-chinmo pathway regulates dietary restriction-dependent enhancement of lifespan in Drosophila |
| title_full | miR-125-chinmo pathway regulates dietary restriction-dependent enhancement of lifespan in Drosophila |
| title_fullStr | miR-125-chinmo pathway regulates dietary restriction-dependent enhancement of lifespan in Drosophila |
| title_full_unstemmed | miR-125-chinmo pathway regulates dietary restriction-dependent enhancement of lifespan in Drosophila |
| title_short | miR-125-chinmo pathway regulates dietary restriction-dependent enhancement of lifespan in Drosophila |
| title_sort | mir 125 chinmo pathway regulates dietary restriction dependent enhancement of lifespan in drosophila |
| topic | microRNAs dietary restriction aging miR-125 fat metabolism |
| url | https://elifesciences.org/articles/62621 |
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