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Endogenous DAF-16 Spatiotemporal Activity Quantitatively Predicts Lifespan Extension Induced by Dietary Restriction

Javier Huayta, View ORCID ProfileAdriana San-Miguel
doi: https://doi.org/10.1101/2021.12.20.473576
Javier Huayta
1Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, North Carolina, USA
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Adriana San-Miguel
1Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, North Carolina, USA
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  • ORCID record for Adriana San-Miguel
  • For correspondence: asanmig@ncsu.edu
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Summary

In many organisms, dietary restriction (DR) leads to lifespan extension through the activation of cell protection and pro-longevity gene expression programs. In the nematode C. elegans, the DAF-16 transcription factor is a key aging regulator that governs the Insulin/IGF-1 signaling pathway and undergoes translocation from the cytoplasm to the nucleus of cells when animals are exposed to food limitation. In this work, we assess the endogenous activity of DAF-16 under various DR regimes by coupling CRISPR/Cas9-enabled fluorescent tagging of DAF-16 with quantitative image analysis and machine learning. Our results indicate that lifelong DAF-16 endogenous activity is a robust predictor of mean lifespan in C. elegans, and it accounts for 78% of the lifespan variability induced by DR. We found that this lifespan-extending mechanism occurs mainly in the intestine and neurons, and that DR drives DAF-16 activity in unexpected locations such as the germline and intestinal nucleoli.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted December 21, 2021.
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Endogenous DAF-16 Spatiotemporal Activity Quantitatively Predicts Lifespan Extension Induced by Dietary Restriction
Javier Huayta, Adriana San-Miguel
bioRxiv 2021.12.20.473576; doi: https://doi.org/10.1101/2021.12.20.473576
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Endogenous DAF-16 Spatiotemporal Activity Quantitatively Predicts Lifespan Extension Induced by Dietary Restriction
Javier Huayta, Adriana San-Miguel
bioRxiv 2021.12.20.473576; doi: https://doi.org/10.1101/2021.12.20.473576

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