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The conserved microRNA‐229 family controls low‐insulin signaling and dietary restriction induced longevity through interactions with SKN‐1/NRF2
Several microRNAs have emerged as regulators of pathways that control aging. For example, miR‐228 is required for normal lifespan and dietary restriction (DR) mediated longevity through interaction with PHA‐4 and SKN‐1 transcription factors in Caenorhabditis elegans. miR‐229,64,65, and 66, a cluster...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10086521/ https://www.ncbi.nlm.nih.gov/pubmed/36748780 http://dx.doi.org/10.1111/acel.13785 |
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author | Matai, Latika Stathis, Thalyana Lee, Jonathan D. Parsons, Christine Saxena, Tanvi Shlomchik, Kovi Slack, Frank J. |
author_facet | Matai, Latika Stathis, Thalyana Lee, Jonathan D. Parsons, Christine Saxena, Tanvi Shlomchik, Kovi Slack, Frank J. |
author_sort | Matai, Latika |
collection | PubMed |
description | Several microRNAs have emerged as regulators of pathways that control aging. For example, miR‐228 is required for normal lifespan and dietary restriction (DR) mediated longevity through interaction with PHA‐4 and SKN‐1 transcription factors in Caenorhabditis elegans. miR‐229,64,65, and 66, a cluster of microRNAs located adjacent to each other on chromosome III, are in the same family as miR‐228, albeit with slight differences in the miR‐228 seed sequence. We demonstrate that, in contrast to the anti‐longevity role of miR‐228, the miR‐229‐66 cluster is required for normal C. elegans lifespan and for the longevity observed in mir‐228 mutants. miR‐229‐66 is also critical for lifespan extension observed under DR and reduced insulin signaling (IIS) and by constitutive nuclear SKN‐1. Both DR and low‐IIS upregulate the expression of the miRNA cluster, which is dependent on transcription factors PHA‐4, SKN‐1, and DAF‐16. In turn, the expression of SKN‐1 and DAF‐16 requires mir‐229,64,65,66. miR‐229‐66 targets the odd‐skipped‐related transcription factor, odd‐2 to regulate lifespan. Knockdown of odd‐2 increases lifespan, suppresses the short lifespan of mir‐229,64,65,66(nDf63) III mutants, and alters levels of SKN‐1 in the ASI neurons. Together with SKN‐1, the miRNA cluster also indirectly regulates several genes in the xenobiotic detoxification pathway which increases wild‐type lifespan and significantly rescues the short lifespan of mir‐229,64,65,66(nDf63) III mutants. Thus, by interacting with SKN‐1, miR‐229‐66 transduces the effects of DR and low‐IIS in lifespan extension in C. elegans. Given that this pathway is conserved, it is possible that a similar mechanism regulates aging in more complex organisms. |
format | Online Article Text |
id | pubmed-10086521 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-100865212023-04-12 The conserved microRNA‐229 family controls low‐insulin signaling and dietary restriction induced longevity through interactions with SKN‐1/NRF2 Matai, Latika Stathis, Thalyana Lee, Jonathan D. Parsons, Christine Saxena, Tanvi Shlomchik, Kovi Slack, Frank J. Aging Cell Research Articles Several microRNAs have emerged as regulators of pathways that control aging. For example, miR‐228 is required for normal lifespan and dietary restriction (DR) mediated longevity through interaction with PHA‐4 and SKN‐1 transcription factors in Caenorhabditis elegans. miR‐229,64,65, and 66, a cluster of microRNAs located adjacent to each other on chromosome III, are in the same family as miR‐228, albeit with slight differences in the miR‐228 seed sequence. We demonstrate that, in contrast to the anti‐longevity role of miR‐228, the miR‐229‐66 cluster is required for normal C. elegans lifespan and for the longevity observed in mir‐228 mutants. miR‐229‐66 is also critical for lifespan extension observed under DR and reduced insulin signaling (IIS) and by constitutive nuclear SKN‐1. Both DR and low‐IIS upregulate the expression of the miRNA cluster, which is dependent on transcription factors PHA‐4, SKN‐1, and DAF‐16. In turn, the expression of SKN‐1 and DAF‐16 requires mir‐229,64,65,66. miR‐229‐66 targets the odd‐skipped‐related transcription factor, odd‐2 to regulate lifespan. Knockdown of odd‐2 increases lifespan, suppresses the short lifespan of mir‐229,64,65,66(nDf63) III mutants, and alters levels of SKN‐1 in the ASI neurons. Together with SKN‐1, the miRNA cluster also indirectly regulates several genes in the xenobiotic detoxification pathway which increases wild‐type lifespan and significantly rescues the short lifespan of mir‐229,64,65,66(nDf63) III mutants. Thus, by interacting with SKN‐1, miR‐229‐66 transduces the effects of DR and low‐IIS in lifespan extension in C. elegans. Given that this pathway is conserved, it is possible that a similar mechanism regulates aging in more complex organisms. John Wiley and Sons Inc. 2023-02-07 /pmc/articles/PMC10086521/ /pubmed/36748780 http://dx.doi.org/10.1111/acel.13785 Text en © 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Matai, Latika Stathis, Thalyana Lee, Jonathan D. Parsons, Christine Saxena, Tanvi Shlomchik, Kovi Slack, Frank J. The conserved microRNA‐229 family controls low‐insulin signaling and dietary restriction induced longevity through interactions with SKN‐1/NRF2 |
title | The conserved microRNA‐229 family controls low‐insulin signaling and dietary restriction induced longevity through interactions with SKN‐1/NRF2
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title_full | The conserved microRNA‐229 family controls low‐insulin signaling and dietary restriction induced longevity through interactions with SKN‐1/NRF2
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title_fullStr | The conserved microRNA‐229 family controls low‐insulin signaling and dietary restriction induced longevity through interactions with SKN‐1/NRF2
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title_full_unstemmed | The conserved microRNA‐229 family controls low‐insulin signaling and dietary restriction induced longevity through interactions with SKN‐1/NRF2
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title_short | The conserved microRNA‐229 family controls low‐insulin signaling and dietary restriction induced longevity through interactions with SKN‐1/NRF2
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title_sort | conserved microrna‐229 family controls low‐insulin signaling and dietary restriction induced longevity through interactions with skn‐1/nrf2 |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10086521/ https://www.ncbi.nlm.nih.gov/pubmed/36748780 http://dx.doi.org/10.1111/acel.13785 |
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