Tiku, Varnesh, Jain, Chirag, Raz, Yotam ORCID: 0000-0001-9628-632X, Nakamura, Shuhei, Heestand, Bree, Liu, Wei, Spaeth, Martin, Suchiman, H. Eka. D., Mueller, Roman-Ulrich, Slagboom, P. Eline, Partridge, Linda ORCID: 0000-0001-9615-0094 and Antebi, Adam (2017). Small nucleoli are a cellular hallmark of longevity. Nat. Commun., 8. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Tiku, VarneshUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jain, ChiragUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Raz, YotamUNSPECIFIEDorcid.org/0000-0001-9628-632XUNSPECIFIED
Nakamura, ShuheiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heestand, BreeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liu, WeiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Spaeth, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Suchiman, H. Eka. D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller, Roman-UlrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Slagboom, P. ElineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Partridge, LindaUNSPECIFIEDorcid.org/0000-0001-9615-0094UNSPECIFIED
Antebi, AdamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-221385
DOI: 10.1038/ncomms16083
Journal or Publication Title: Nat. Commun.
Volume: 8
Date: 2017
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2041-1723
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
LIFE-SPAN EXTENSION; CAENORHABDITIS-ELEGANS; C-ELEGANS; INHIBITION; GENES; YEAST; TRANSLATION; DETERMINANT; BIOMARKERS; GENETICSMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/22138

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