Tiku, V;
Jain, C;
Raz, Y;
Nakamura, S;
Heestand, B;
Liu, W;
Späth, M;
... Antebi, A; + view all
(2017)
Small nucleoli are a cellular hallmark of longevity.
Nature Communications
, 8
, Article 16083. 10.1038/ncomms16083.
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Abstract
Animal lifespan is regulated by conserved metabolic signalling pathways and specific transcription factors, but whether these pathways affect common downstream mechanisms remains largely elusive. Here we show that NCL-1/TRIM2/Brat tumour suppressor extends lifespan and limits nucleolar size in the major C. elegans longevity pathways, as part of a convergent mechanism focused on the nucleolus. Long-lived animals representing distinct longevity pathways exhibit small nucleoli, and decreased expression of rRNA, ribosomal proteins, and the nucleolar protein fibrillarin, dependent on NCL-1. Knockdown of fibrillarin also reduces nucleolar size and extends lifespan. Among wildtype C. elegans, individual nucleolar size varies, but is highly predictive for longevity. Long-lived dietary restricted fruit flies and insulin-like-peptide mutants exhibit small nucleoli and fibrillarin expression, as do long-lived dietary restricted and IRS1 knockout mice. Furthermore, human muscle biopsies from individuals who underwent modest dietary restriction coupled with exercise also display small nucleoli. We suggest that small nucleoli are a cellular hallmark of longevity and metabolic health conserved across taxa.
| Type: | Article |
|---|---|
| Title: | Small nucleoli are a cellular hallmark of longevity |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/ncomms16083 |
| Publisher version: | https://doi.org/10.1038/ncomms16083 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Caloric Restriction, Carrier Proteins, Cell Nucleolus, Chromosomal Proteins, Non-Histone, Drosophila, Exercise, Gene Knockdown Techniques, Humans, Insulin Receptor Substrate Proteins, Longevity, Metabolic Networks and Pathways, Mice, Knockout, Muscle, Skeletal, Organelle Biogenesis, Organelle Size, RNA, Ribosomal, Ribosomal Proteins, Ribosomes |
| 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/10065974 |
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