Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Tiku, Varnesh UNSPECIFIED UNSPECIFIED UNSPECIFIED Jain, Chirag UNSPECIFIED UNSPECIFIED UNSPECIFIED Raz, Yotam UNSPECIFIED orcid.org/0000-0001-9628-632X UNSPECIFIED Nakamura, Shuhei UNSPECIFIED UNSPECIFIED UNSPECIFIED Heestand, Bree UNSPECIFIED UNSPECIFIED UNSPECIFIED Liu, Wei UNSPECIFIED UNSPECIFIED UNSPECIFIED Spaeth, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Suchiman, H. Eka. D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Roman-Ulrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Slagboom, P. Eline UNSPECIFIED UNSPECIFIED UNSPECIFIED Partridge, Linda UNSPECIFIED orcid.org/0000-0001-9615-0094 UNSPECIFIED Antebi, Adam UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language LIFE-SPAN EXTENSION; CAENORHABDITIS-ELEGANS; C-ELEGANS; INHIBITION; GENES; YEAST; TRANSLATION; DETERMINANT; BIOMARKERS; GENETICS Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22138