The insulin/IGF signaling cascade modulates SUMOylation to regulate aging and proteostasis in Caenorhabditis elegans

• Published in: eLife Vol. 7
• Main Authors: Moll, Lorna, Roitenberg, Noa, Bejerano-Sagie, Michal, Boocholez, Hana, Carvalhal Marques, Filipa, Volovik, Yuli, Elami, Tayir, Siddiqui, Atif Ahmed, Grushko, Danielle, Biram, Adi, Lampert, Bar, Achache, Hana, Ravid, Tommer, Tzur, Yonatan B, Cohen, Ehud
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications Ltd 07.11.2018; eLife Sciences Publications, Ltd
• Subjects: Aging; Aging - metabolism; Animals; Apoptosis; Bacteria; Caenorhabditis elegans; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - metabolism; Cell Biology; Eggs; Gene Knockdown Techniques; Germ Cells - metabolism; germline; Gonads - metabolism; Insulin; Insulin - metabolism; Insulin-Like Growth Factor I - metabolism; Insulin-like growth factors; insulin/IGF signaling; Life sciences; Life span; lifespan; Longevity; Models, Biological; Nematodes; Neuroscience; Notch-like receptor; Phosphorylation; Proteins; Proteostasis; Signal Transduction; Stress, Physiological; SUMO protein; SUMOylation; Transcription factors; Transcription, Genetic; Worms; Jerusalem Israel; Israel; insulin/IGF signaling; C. elegans; cell biology; germline; lifespan; neuroscience; SUMOylation; aging; proteostasis
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.38635

Although aging-regulating pathways were discovered a few decades ago, it is not entirely clear how their activities are orchestrated, to govern lifespan and proteostasis at the organismal level. Here, we utilized the nematode to examine whether the alteration of aging, by reducing the activity of the Insulin/IGF signaling (IIS) cascade, affects protein SUMOylation. We found that IIS activity promotes the SUMOylation of the germline protein, CAR-1, thereby shortening lifespan and impairing proteostasis. In contrast, the expression of mutated CAR-1, that cannot be SUMOylated at residue 185, extends lifespan and enhances proteostasis. A mechanistic analysis indicated that CAR-1 mediates its aging-altering functions, at least partially, through the notch-like receptor . Our findings unveil a novel regulatory axis in which SUMOylation is utilized to integrate the aging-controlling functions of the IIS and of the germline and provide new insights into the roles of SUMOylation in the regulation of organismal aging.