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Temperature-dependent lifespan extension is achieved in miR-80-deleted Caenorhabditis elegans by NLP-45 to modulate endoplasmic reticulum unfolded protein responses.

Chunlin Zhao | Jintao Luo | Yuqiang Zhang | Yong Yu
Aging cell | 2025

MicroRNA plays a crucial role in post-transcriptional gene regulation and has recently emerged as a factor linked to aging, but the underlying regulatory mechanisms remain incompletely understood. In this study, we observed lifespan-extending effects in miR-80-deficient Caenorhabditis elegans at 20°C but not 25°C. At 20°C, miR-80 deletion leads to NLP-45 upregulation, which positively correlates to increased abu transcripts and extended lifespan. Supportively, we identified miR-80 binding regions in the 5' and 3' UTR of nlp-45. As the temperature rises to 25°C, wildtype increases miR-80 levels, but removal of miR-80 is accompanied by decreased nlp-45 expression, suggesting intervention from other temperature-sensitive mechanisms. These findings support the concept that microRNAs and neuropeptide-like proteins can form molecular regulatory networks involving downstream molecules to regulate lifespan, and such regulatory effects vary on environmental conditions. This study unveils the role of an axis of miR-80/NLP-45/UPRER components in regulating longevity, offering new insights on strategies of aging attenuation and health span prolongation.

Pubmed ID: 39323014

Associated grants

  • Agency: NIH HHS, United States
    Id: P40 OD010440
  • Agency: Natural Science Foundation of Fujian Province of China,
    Id: 2024J01025
  • Agency: National Natural Science Foundation of China,
    Id: 32071146
  • Agency: Fundamental Research Funds for the Central Universities,
    Id: 20720230066
  • Agency: Xiamen University Training Program of Innovation and Enterpreneurship for Undergraduates,
    Id: 2021X1185
  • Agency: Natural Science Foundation of Fujian Province of China,
    Id: 2023J05007
  • Agency: Fundamental Research Funds for the Central Universities,
    Id: 20720222015

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NCBI Sequence Read Archive (SRA) (tool)

RRID:SCR_004891

Repository of raw sequencing data from next generation of sequencing platforms including including Roche 454 GS System, Illumina Genome Analyzer, Applied Biosystems SOLiD System, Helicos Heliscope, Complete Genomics, and Pacific Biosciences SMRT. In addition to raw sequence data, SRA now stores alignment information in form of read placements on reference sequence. Data submissions are welcome. Archive of high throughput sequencing data,part of international partnership of archives (INSDC) at NCBI, European Bioinformatics Institute and DNA Database of Japan. Data submitted to any of this three organizations are shared among them.

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Caenorhabditis Genetics Center (biomaterial supply resource)

RRID:SCR_007341

Center that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.

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PS8027 (organism)

RRID:WB-STRAIN:WBStrain00031058

Caenorhabditis elegans with name nlp-67(sy1176) X. from WB.

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OP506 (organism)

RRID:WB-STRAIN:WBStrain00030284

Caenorhabditis elegans with name unc-119(tm4063) III; wgIs506. from WB.

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VC461 (organism)

RRID:WB-STRAIN:WBStrain00035788

Caenorhabditis elegans with name egl-3(gk238) V. from WB.

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SJ4005 (organism)

RRID:WB-STRAIN:WBStrain00034065

Caenorhabditis elegans with name zcIs4 V. from WB.

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OP683 (organism)

RRID:WB-STRAIN:WBStrain00030422

Caenorhabditis elegans with name unc-119(tm4063) III; wgIs683. from WB.

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MT13954 (organism)

RRID:WB-STRAIN:WBStrain00027445

Caenorhabditis elegans with name mir-81&mir-82(nDf54) X. from WB.

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Caenorhabditis Genetics Center (biomaterial supply resource)

RRID:SCR_007341

Center that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.

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MT13949 (organism)

RRID:WB-STRAIN:WBStrain00027443

Caenorhabditis elegans with name mir-80(nDf53) III. from WB.

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MT15024 (organism)

RRID:WB-STRAIN:WBStrain00027508

Caenorhabditis elegans with name mir-58.1(n4640) IV. from WB.

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DA509 (organism)

RRID:WB-STRAIN:WBStrain00005475

Caenorhabditis elegans with name unc-31(e928) IV. from WB.

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Caenorhabditis Genetics Center (biomaterial supply resource)

RRID:SCR_007341

Center that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.

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