Malik, Yasir;
Goncalves Silva, Isabel;
Diazgranados, Rene Rivera;
Selman, Colin;
Alic, Nazif;
Tullet, Jennifer Ma;
(2024)
Timing of TORC1 inhibition dictates Pol III involvement in Caenorhabditis elegans longevity.
Life Science Alliance
, 7
(7)
, Article e202402735. 10.26508/lsa.202402735.
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Abstract
Organismal growth and lifespan are inextricably linked. Target of Rapamycin (TOR) signalling regulates protein production for growth and development, but if reduced, extends lifespan across species. Reduction in the enzyme RNA polymerase III, which transcribes tRNAs and 5S rRNA, also extends longevity. Here, we identify a temporal genetic relationship between TOR and Pol III in Caenorhabditis elegans, showing that they collaborate to regulate progeny production and lifespan. Interestingly, the lifespan interaction between Pol III and TOR is only revealed when TOR signaling is reduced, specifically in adulthood, demonstrating the importance of timing to control TOR regulated developmental versus adult programs. In addition, we show that Pol III acts in C. elegans muscle to promote both longevity and healthspan and that reducing Pol III even in late adulthood is sufficient to extend lifespan. This demonstrates the importance of Pol III for lifespan and age-related health in adult C. elegans.
| Type: | Article |
|---|---|
| Title: | Timing of TORC1 inhibition dictates Pol III involvement in Caenorhabditis elegans longevity |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.26508/lsa.202402735 |
| Publisher version: | http://dx.doi.org/10.26508/lsa.202402735 |
| Language: | English |
| Additional information: | This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/ licenses/by/4.0/). |
| Keywords: | Animals, Caenorhabditis elegans, Longevity, RNA Polymerase III, Mechanistic Target of Rapamycin Complex 1, Caenorhabditis elegans Proteins, Signal Transduction, TOR Serine-Threonine Kinases, Aging |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10192473 |
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