%0 Journal Article
%A Lechler, Marie C
%A Crawford, Emily D
%A Groh, Nicole
%A Widmaier, Katja
%A Jung, Raimund
%A Kirstein, Janine
%A Trinidad, Jonathan C
%A Burlingame, Alma L
%A David, Della
%T Reduced Insulin/IGF-1 Signaling Restores the Dynamic Properties of Key Stress Granule Proteins during Aging.
%J Cell reports
%V 18
%N 2
%@ 2211-1247
%C [New York, NY]
%I Elsevier
%M DZNE-2020-05435
%P 454-467
%D 2017
%X Low-complexity 'prion-like' domains in key RNA-binding proteins (RBPs) mediate the reversible assembly of RNA granules. Individual RBPs harboring these domains have been linked to specific neurodegenerative diseases. Although their aggregation in neurodegeneration has been extensively characterized, it remains unknown how the process of aging disturbs RBP dynamics. We show that a wide variety of RNA granule components, including stress granule proteins, become highly insoluble with age in C. elegans and that reduced insulin/insulin-like growth factor 1 (IGF-1) daf-2 receptor signaling efficiently prevents their aggregation. Importantly, stress-granule-related RBP aggregates are associated with reduced fitness. We show that heat shock transcription factor 1 (HSF-1) is a main regulator of stress-granule-related RBP aggregation in both young and aged animals. During aging, increasing DAF-16 activity restores dynamic stress-granule-related RBPs, partly by decreasing the buildup of other misfolded proteins that seed RBP aggregation. Longevity-associated mechanisms found to maintain dynamic RBPs during aging could be relevant for neurodegenerative diseases.
%K Aging: metabolism
%K Animals
%K Caenorhabditis elegans: metabolism
%K Caenorhabditis elegans Proteins: metabolism
%K Cytoplasmic Granules: metabolism
%K Heat-Shock Proteins: metabolism
%K Insulin: metabolism
%K Insulin-Like Growth Factor I: metabolism
%K Longevity
%K Mutation: genetics
%K Protein Aggregates
%K RNA: metabolism
%K RNA-Binding Proteins: metabolism
%K Receptor, Insulin: metabolism
%K Signal Transduction
%K Solubility
%K Caenorhabditis elegans Proteins (NLM Chemicals)
%K Heat-Shock Proteins (NLM Chemicals)
%K Insulin (NLM Chemicals)
%K Protein Aggregates (NLM Chemicals)
%K RNA-Binding Proteins (NLM Chemicals)
%K RNA (NLM Chemicals)
%K Insulin-Like Growth Factor I (NLM Chemicals)
%K DAF-2 protein, C elegans (NLM Chemicals)
%K Receptor, Insulin (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:28076789
%2 pmc:PMC5263236
%R 10.1016/j.celrep.2016.12.033
%U https://pub.dzne.de/record/139113