Reduced insulin/IGF-1 signaling restores the dynamic properties of key stress granule proteins during aging

ABSTRACT: 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/IGF-1 daf-2 receptor signaling efficiently prevents their aggregation. Importantly, stress granule-related RBP aggregates are associated with reduced fitness. We show that 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 reducing the build-up of other misfolded proteins that seed RBP aggregation. Longevity-associated mechanisms found to maintain dynamic RBPs during aging could be relevant for neurodegenerative diseases.

INSTRUMENT(S):

ORGANISM(S): Caenorhabditis Elegans

TISSUE(S): Whole Body

DISEASE(S): Disease Free

SUBMITTER: Jonathan Trinidad  

LAB HEAD: Della C. David

PROVIDER: PXD003451 | Pride | 2017-01-16

REPOSITORIES: Pride