eprintid: 10065974
rev_number: 16
eprint_status: archive
userid: 608
dir: disk0/10/06/59/74
datestamp: 2019-01-17 11:46:47
lastmod: 2021-09-19 22:52:41
status_changed: 2019-01-17 11:46:47
type: article
metadata_visibility: show
creators_name: Tiku, V
creators_name: Jain, C
creators_name: Raz, Y
creators_name: Nakamura, S
creators_name: Heestand, B
creators_name: Liu, W
creators_name: Späth, M
creators_name: Suchiman, HED
creators_name: Müller, R-U
creators_name: Slagboom, PE
creators_name: Partridge, L
creators_name: Antebi, A
title: Small nucleoli are a cellular hallmark of longevity
ispublished: pub
divisions: UCL
divisions: B02
divisions: C08
divisions: D09
divisions: F99
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
note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
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.
date: 2017-08-30
date_type: published
official_url: https://doi.org/10.1038/ncomms16083
oa_status: green
full_text_type: pub
pmcid: PMC5582349
language: eng
primo: open
primo_central: open_green
article_type_text: Journal Article
verified: verified_manual
elements_id: 1616668
doi: 10.1038/ncomms16083
pii: ncomms16083
lyricists_name: Partridge, Linda
lyricists_id: LPART24
actors_name: Flynn, Bernadette
actors_id: BFFLY94
actors_role: owner
full_text_status: public
publication: Nature Communications
volume: 8
article_number: 16083
event_location: England
issn: 2041-1723
citation:        Tiku, V;    Jain, C;    Raz, Y;    Nakamura, S;    Heestand, B;    Liu, W;    Späth, M;                     ... Antebi, A; + view all <#>        Tiku, V;  Jain, C;  Raz, Y;  Nakamura, S;  Heestand, B;  Liu, W;  Späth, M;  Suchiman, HED;  Müller, R-U;  Slagboom, PE;  Partridge, L;  Antebi, A;   - view fewer <#>    (2017)    Small nucleoli are a cellular hallmark of longevity.                   Nature Communications , 8     , Article 16083.  10.1038/ncomms16083 <https://doi.org/10.1038/ncomms16083>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10065974/1/ncomms16083.pdf