TY  - JOUR
AV  - public
N2  - 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.
KW  - Animals
KW  -  Caenorhabditis elegans
KW  -  Caenorhabditis elegans Proteins
KW  -  Caloric Restriction
KW  -  Carrier Proteins
KW  -  Cell Nucleolus
KW  -  Chromosomal Proteins
KW  -  Non-Histone
KW  -  Drosophila
KW  -  Exercise
KW  -  Gene Knockdown Techniques
KW  -  Humans
KW  -  Insulin Receptor Substrate Proteins
KW  -  Longevity
KW  -  Metabolic Networks and Pathways
KW  -  Mice
KW  -  Knockout
KW  -  Muscle
KW  -  Skeletal
KW  -  Organelle Biogenesis
KW  -  Organelle Size
KW  -  RNA
KW  -  Ribosomal
KW  -  Ribosomal Proteins
KW  -  Ribosomes
SN  - 2041-1723
A1  - Tiku, V
A1  - Jain, C
A1  - Raz, Y
A1  - Nakamura, S
A1  - Heestand, B
A1  - Liu, W
A1  - Späth, M
A1  - Suchiman, HED
A1  - Müller, R-U
A1  - Slagboom, PE
A1  - Partridge, L
A1  - Antebi, A
VL  - 8
JF  - Nature Communications
N1  - This version is the author accepted manuscript. For information on re-use, please refer to the publisher?s terms and conditions.
TI  - Small nucleoli are a cellular hallmark of longevity
Y1  - 2017/08/30/
UR  - https://doi.org/10.1038/ncomms16083
ID  - discovery10065974
ER  -