Nucleolar expansion and elevated protein translation in premature aging

Abigail Buchwalter and Martin W. Hetzer ()
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Abigail Buchwalter: The Salk Institute for Biological Studies
Martin W. Hetzer: The Salk Institute for Biological Studies

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: Abstract Premature aging disorders provide an opportunity to study the mechanisms that drive aging. In Hutchinson-Gilford progeria syndrome (HGPS), a mutant form of the nuclear scaffold protein lamin A distorts nuclei and sequesters nuclear proteins. We sought to investigate protein homeostasis in this disease. Here, we report a widespread increase in protein turnover in HGPS-derived cells compared to normal cells. We determine that global protein synthesis is elevated as a consequence of activated nucleoli and enhanced ribosome biogenesis in HGPS-derived fibroblasts. Depleting normal lamin A or inducing mutant lamin A expression are each sufficient to drive nucleolar expansion. We further show that nucleolar size correlates with donor age in primary fibroblasts derived from healthy individuals and that ribosomal RNA production increases with age, indicating that nucleolar size and activity can serve as aging biomarkers. While limiting ribosome biogenesis extends lifespan in several systems, we show that increased ribosome biogenesis and activity are a hallmark of premature aging.

Date: 2017
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DOI: 10.1038/s41467-017-00322-z

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