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Journal Article

Small nucleoli are a cellular hallmark of longevity

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Tiku,  V.
Department Antebi - Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

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Jain,  C.
Department Partridge - Biological Mechanisms of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

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Slagboom,  P. E.
Slagboom – Molecular Epidemiology, External and Associated Groups, Max Planck Institute for Biology of Ageing, Max Planck Society;

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Partridge,  L.
Department Partridge - Biological Mechanisms of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

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Antebi,  A.
Department Antebi - Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

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Citation

Tiku, V., Jain, C., Raz, Y., Nakamura, S., Heestand, B., Liu, W., et al. (2017). Small nucleoli are a cellular hallmark of longevity. Nat Commun, 8, 16083. doi:10.1038/ncomms16083.


Cite as: https://hdl.handle.net/21.11116/0000-000B-4A7B-9
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.