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2017 ; 8
(ä): 16083
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Small nucleoli are a cellular hallmark of longevity
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Tiku V
; Jain C
; Raz Y
; Nakamura S
; Heestand B
; Liu W
; Späth M
; Suchiman HED
; Müller RU
; Slagboom PE
; Partridge L
; Antebi A
Nat Commun
2017[Aug]; 8
(ä): 16083
PMID28853436
show ga
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.
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