2023 journal article

Endogenous DAF-16 spatiotemporal activity quantitatively predicts lifespan extension induced by dietary restriction

COMMUNICATIONS BIOLOGY, 6(1).

By: J. Huayta  n, J. Crapster  n & A. San-Miguel  n

MeSH headings : Animals; Caenorhabditis elegans / genetics; Longevity / genetics; Caenorhabditis elegans Proteins / metabolism; Signal Transduction; Insulin / metabolism; Forkhead Transcription Factors / metabolism
TL;DR: The results indicate that DR regimes induce strong endogenous DAF-16 activity, although Daf-16 is less responsive in aged individuals, and analysis of tissue-specific expression aided by a machine learning tissue classifier reveals that, under DR, the largest contribution to D AF-16 nuclear intensity originates from the intestine and neurons. (via Semantic Scholar)
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Source: Web Of Science
Added: March 27, 2023

AbstractIn 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. However, how large is the influence of DR on DAF-16 activity, and its subsequent impact on lifespan has not been quantitatively determined. 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 DR regimes induce strong endogenous DAF-16 activity, although DAF-16 is less responsive in aged individuals. DAF-16 activity is in turn a robust predictor of mean lifespan in C. elegans, accounting for 78% of its variability under DR. Analysis of tissue-specific expression aided by a machine learning tissue classifier reveals that, under DR, the largest contribution to DAF-16 nuclear intensity originates from the intestine and neurons. DR also drives DAF-16 activity in unexpected locations such as the germline and intestinal nucleoli.