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Dauer-independent insulin/IGF-1-signalling implicates collagen remodelling in longevity
Collin Y Ewald1, Jess N Landis2, Jess Porter Abate1
11] Joslin Diabetes Center, One Joslin Place, Boston, Massachusetts 02215, USA [2] Harvard Stem Cell Institute, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA [3] Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02215, USA.
Nature
|December 18, 2014
Summary
Reduced insulin/IGF-1 signaling (rIIS) extends lifespan in C. elegans via a pathway independent of dauer, utilizing SKN-1 to boost collagen production and maintain extracellular matrix youthfulness for longevity.
Area of Science:
- Gerontology
- Molecular Biology
- Biochemistry
Background:
- Aging involves cellular damage and extracellular matrix (ECM) decline.
- Reduced insulin/IGF-1 signaling (rIIS) extends lifespan but its ECM effects are unclear.
- The dauer pathway is linked to rIIS lifespan extension, but alternative mechanisms exist.
Purpose of the Study:
- To investigate how rIIS affects ECM during aging.
- To identify aging pathways independent of dauer.
- To explore the role of SKN-1 in rIIS-mediated longevity and ECM maintenance.
Main Methods:
- Utilized Caenorhabditis elegans as a model organism.
- Employed genetic manipulation to study rIIS, DAF-16, and SKN-1 pathways.
- Analyzed gene expression, focusing on collagens and ECM components.
- Assessed lifespan under various genetic and environmental conditions.
Main Results:
- rIIS promotes C. elegans longevity through a dauer-independent pathway involving SKN-1.
- SKN-1, when activated by low IIS without dauer traits, upregulates collagen and ECM gene expression.
- Diverse pro-longevity interventions delay age-related decline in collagen expression.
- Collagen-mediated ECM remodeling is essential for lifespan extension in dauer-independent rIIS pathways.
Conclusions:
- IIS regulates diverse protective mechanisms in adult C. elegans.
- A dauer-independent pathway involving SKN-1 and ECM remodeling contributes to longevity.
- Maintaining ECM youthfulness is crucial for the efficacy of various anti-aging interventions.
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