TY - JOUR
T1 - Modulation of caveolae by insulin/IGF-1 signaling regulates aging of Caenorhabditis elegans
AU - Roitenberg, Noa
AU - Bejerano-Sagie, Michal
AU - Boocholez, Hana
AU - Moll, Lorna
AU - Marques, Filipa Carvalhal
AU - Golodetzki, Ludmila
AU - Nevo, Yuval
AU - Elami, Tayir
AU - Cohen, Ehud
N1 - Publisher Copyright:
© 2018 The Authors
PY - 2018/8
Y1 - 2018/8
N2 - 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.
AB - 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.
KW - aging
KW - caveolae
KW - insulin/IGF-1 signaling
KW - lifespan
KW - proteostasis
UR - http://www.scopus.com/inward/record.url?scp=85051079033&partnerID=8YFLogxK
U2 - 10.15252/embr.201745673
DO - 10.15252/embr.201745673
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C2 - 29945933
AN - SCOPUS:85051079033
SN - 1469-221X
VL - 19
JO - EMBO Reports
JF - EMBO Reports
IS - 8
M1 - e45673
ER -