Modulation of caveolae by insulin/IGF-1 signaling regulates aging of Caenorhabditis elegans

作者:Roitenberg Noa; Bejerano Sagie Michal; Boocholez Hana; Moll Lorna; Marques Filipa Carvalhal; Golodetzki Ludmila; Nevo Yuval; Elami Tayir; Cohen Ehud*
来源:EMBO Reports, 2018, 19(8): UNSP e45673.
DOI:10.15252/embr.201745673

摘要

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.