TY  - JOUR
AU  - Lechler, Marie C
AU  - Crawford, Emily D
AU  - Groh, Nicole
AU  - Widmaier, Katja
AU  - Jung, Raimund
AU  - Kirstein, Janine
AU  - Trinidad, Jonathan C
AU  - Burlingame, Alma L
AU  - David, Della
TI  - Reduced Insulin/IGF-1 Signaling Restores the Dynamic Properties of Key Stress Granule Proteins during Aging.
JO  - Cell reports
VL  - 18
IS  - 2
SN  - 2211-1247
CY  - [New York, NY]
PB  - Elsevier
M1  - DZNE-2020-05435
SP  - 454-467
PY  - 2017
AB  - 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.
KW  - Aging: metabolism
KW  - Animals
KW  - Caenorhabditis elegans: metabolism
KW  - Caenorhabditis elegans Proteins: metabolism
KW  - Cytoplasmic Granules: metabolism
KW  - Heat-Shock Proteins: metabolism
KW  - Insulin: metabolism
KW  - Insulin-Like Growth Factor I: metabolism
KW  - Longevity
KW  - Mutation: genetics
KW  - Protein Aggregates
KW  - RNA: metabolism
KW  - RNA-Binding Proteins: metabolism
KW  - Receptor, Insulin: metabolism
KW  - Signal Transduction
KW  - Solubility
KW  - Caenorhabditis elegans Proteins (NLM Chemicals)
KW  - Heat-Shock Proteins (NLM Chemicals)
KW  - Insulin (NLM Chemicals)
KW  - Protein Aggregates (NLM Chemicals)
KW  - RNA-Binding Proteins (NLM Chemicals)
KW  - RNA (NLM Chemicals)
KW  - Insulin-Like Growth Factor I (NLM Chemicals)
KW  - DAF-2 protein, C elegans (NLM Chemicals)
KW  - Receptor, Insulin (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:28076789
C2  - pmc:PMC5263236
DO  - DOI:10.1016/j.celrep.2016.12.033
UR  - https://pub.dzne.de/record/139113
ER  -