TY - JOUR AV - public N2 - 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. KW - Animals KW - Caenorhabditis elegans KW - Caenorhabditis elegans Proteins KW - Caloric Restriction KW - Carrier Proteins KW - Cell Nucleolus KW - Chromosomal Proteins KW - Non-Histone KW - Drosophila KW - Exercise KW - Gene Knockdown Techniques KW - Humans KW - Insulin Receptor Substrate Proteins KW - Longevity KW - Metabolic Networks and Pathways KW - Mice KW - Knockout KW - Muscle KW - Skeletal KW - Organelle Biogenesis KW - Organelle Size KW - RNA KW - Ribosomal KW - Ribosomal Proteins KW - Ribosomes SN - 2041-1723 A1 - Tiku, V A1 - Jain, C A1 - Raz, Y A1 - Nakamura, S A1 - Heestand, B A1 - Liu, W A1 - Späth, M A1 - Suchiman, HED A1 - Müller, R-U A1 - Slagboom, PE A1 - Partridge, L A1 - Antebi, A VL - 8 JF - Nature Communications N1 - This version is the author accepted manuscript. For information on re-use, please refer to the publisher?s terms and conditions. TI - Small nucleoli are a cellular hallmark of longevity Y1 - 2017/08/30/ UR - https://doi.org/10.1038/ncomms16083 ID - discovery10065974 ER -