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

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 th...

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Bibliographic Details
Published in:eLife 2018-11, 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: Article
Language:English
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
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Summary: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.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.38635