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Journal Article
Small nucleoli are a cellular hallmark of longevity
2017
Overview
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.
Animal lifespan is plastic and is regulated by conserved signalling pathways. Here, Tiku
et al.
show that longevity-enhancing mutations or interventions are associated with reduced nucleolar size in worms, flies, mice and humans, and that nucleolar size can predict life-expectancy in individual worms.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 38/35
/ 38/39
/ 38/89
/ 38/90
/ 82
/ 82/1
/ Animals
/ Caenorhabditis elegans Proteins - genetics
/ Chromosomal Proteins, Non-Histone - genetics
/ Exercise
/ Humanities and Social Sciences
/ Humans
/ Insulin
/ Insulin Receptor Substrate Proteins - genetics
/ Metabolic Networks and Pathways
/ Nucleoli
/ Proteins
/ Ribosomal Proteins - genetics
/ Ribosomal Proteins - metabolism
/ rRNA
/ Science
/ Tumors
