Small nucleoli are a cellular hallmark of longevity

Nature Communications - Tập 8 Số 1
Varnesh Tiku1, Chirag Jain1, Yotam Raz2, Shuhei Nakamura3, Bree Heestand4, Wei Liu5, Martin R. Späth6, H. Eka D. Suchiman2, Roman‐Ulrich Müller6, P. Eline Slagboom2, Linda Partridge6, Adam Antebi6
1Max Planck Institute for Biology of Ageing, Joseph Stelzmann Strasse 9b, Cologne, 50931, Germany
2Section of Molecular Epidemiology, Leiden University Medical Center, Leiden, 2300 RC, The Netherlands
3Department of Genetics, Graduate School of Medicine, Osaka University 2-2 Yamadaoka, Suita, 565-0871, Japan
4Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, 27599-3280, North Carolina, USA
5Department of Molecular and Cellular Biology, Huffington Center on Aging, Baylor College of Medicine, Houston, 77030, Texas, USA
6Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne 50674, Germany

Tóm tắt

AbstractAnimal 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.

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Nature Communications

Tập 8 Số 1

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