RRC ID 54348
Author Roitenberg N, Bejerano-Sagie M, Boocholez H, Moll L, Marques FC, Golodetzki L, Nevo Y, Elami T, Cohen E.
Title Modulation of caveolae by insulin/IGF-1 signaling regulates aging of Caenorhabditis elegans.
Journal EMBO Rep
Abstract Reducing insulin/IGF-1 signaling (IIS) extends lifespan, promotes protein homeostasis (proteostasis), and elevates stress resistance of worms, flies, and mammals. How these functions are orchestrated across the organism is only partially understood. Here, we report that in the nematode Caenorhabditis elegans, the IIS positively regulates the expression of caveolin-1 (cav-1), a gene which is primarily expressed in neurons of the adult worm and underlies the formation of caveolae, a subtype of lipid microdomains that serve as platforms for signaling complexes. Accordingly, IIS reduction lowers cav-1 expression and lessens the quantity of neuronal caveolae. Reduced cav-1 expression extends lifespan and mitigates toxic protein aggregation by modulating the expression of aging-regulating and signaling-promoting genes. Our findings define caveolae as aging-governing signaling centers and underscore the potential for cav-1 as a novel therapeutic target for the promotion of healthy aging.
Volume 19(8)
Published 2018-8-1
DOI 10.15252/embr.201745673
PII embr.201745673
PMID 29945933
PMC PMC6073070
MeSH Aging / metabolism* Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans / ultrastructure Caenorhabditis elegans Proteins / metabolism Caveolae / metabolism* Caveolae / ultrastructure Caveolin 1 / metabolism Caveolin 2 / metabolism Gene Expression Regulation Gene Knockdown Techniques Heat-Shock Response Insulin / metabolism* Insulin-Like Growth Factor I / metabolism* Longevity Models, Biological Proteostasis RNA Interference Signal Transduction* Transcription Factors / metabolism Ultraviolet Rays
IF 8.383
Times Cited 8
C.elegans tm2702