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