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The NO-Age and NO-AD Seminar Series 38 ‘Convergent mechanisms of longevity’ by Prof. Dr. Adam Antebi
Speaker: Adam Antebi, Max Planck Institute for Biology of Ageing, Cologne, Germany

Title: Convergent mechanisms of longevity

Research in model organisms over the last several decades has revealed that animal lifespan is plastic and regulated by conserved metabolic signaling pathways, which work through specific transcription factors to extend life. Whether these pathways affect common downstream mechanisms remains largely elusive. Our studies demonstrate that NCL-1/TRIM2/Brat tumor suppressor extends lifespan and limits nucleolar size in the major C. elegans longevity pathways, as part of a convergent mechanism focused on the nucleolus. Animals representing distinct longevity pathways exhibit small nucleoli, and decreased expression of rRNA, ribosomal proteins, and the nucleolar protein fibrillarin, dependent on NCL-1. Fibrillarin is not only a marker but itself is a causal factor whose knockdown reduces nucleolar size and extends lifespan. Long-lived dietary restricted fruit flies and insulin-like-peptide mutants also exhibit reduced nucleoli and fibrillarin expression. Similarly, tissues derived from long-lived dietary restricted and reduced insulin/IGF signaling IRS1 knockout mice, and humans who undergo modest dietary restriction coupled with exercise display reduced nucleoli. We suggest that small nucleoli are a cellular hallmark of longevity and metabolic health conserved across taxa.

Jun 14, 2021 02:00 PM in Oslo

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