Small nucleoli are a cellular hallmark of longevity

Varnesh Tiku, Chirag Jain, Yotam Raz, Shuhei Nakamura, Bree Heestand, Wei Liu, Martin Späth, H. Eka. D. Suchiman, Roman-Ulrich Müller, P. Eline Slagboom, Linda Partridge and Adam Antebi ()
Additional contact information
Varnesh Tiku: Max Planck Institute for Biology of Ageing
Chirag Jain: Max Planck Institute for Biology of Ageing
Yotam Raz: Section of Molecular Epidemiology, Leiden University Medical Center
Shuhei Nakamura: Graduate School of Medicine
Bree Heestand: Lineberger Comprehensive Cancer Center, University of North Carolina
Wei Liu: Huffington Center on Aging, Baylor College of Medicine
Martin Späth: Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne
H. Eka. D. Suchiman: Section of Molecular Epidemiology, Leiden University Medical Center
Roman-Ulrich Müller: Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne
P. Eline Slagboom: Section of Molecular Epidemiology, Leiden University Medical Center
Linda Partridge: Max Planck Institute for Biology of Ageing
Adam Antebi: Max Planck Institute for Biology of Ageing

Nature Communications, 2017, vol. 8, issue 1, 1-9

Abstract: 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
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DOI: 10.1038/ncomms16083

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