Intestinal Insulin Signaling Encodes Two Different Molecular Mechanisms for the Shortened Longevity Induced by...

Area of Science:

• Toxicology
• Molecular Biology
• Genetics
• Aging Research

Background:

• Graphene oxide (GO) exhibits toxicity across various organisms.
• The molecular mechanisms underlying GO-induced lifespan reduction remain largely unknown.
• The insulin signaling pathway is a critical regulator of aging and stress response.

Purpose of the Study:

• To investigate the role of the insulin signaling pathway in Graphene oxide (GO) toxicity.
• To elucidate the molecular mechanisms by which GO affects longevity in C. elegans.
• To identify specific components of the insulin pathway involved in GO-induced toxicity.

Main Methods:

• Utilized Caenorhabditis elegans (nematode model organism).
• Employed genetic mutations (daf-2, age-1, akt-1, akt-2, daf-16) to assess resistance/susceptibility to GO.
• Performed genetic interaction analysis and intestinal RNA interference (RNAi) to study pathway function.

Main Results:

• Mutations in daf-2, age-1, akt-1, or akt-2 conferred resistance to GO toxicity.
• Mutation in daf-16 resulted in increased susceptibility to GO toxicity.
• The DAF-2/IGF-1 receptor, AGE-1, AKT-1/2 kinase cascade, and DAF-16/FOXO transcription factor are implicated in GO toxicity.
• Intestinal insulin signaling regulates GO's impact on longevity, involving DAF-16's role upstream of the antioxidant SOD-3.

Conclusions:

• The insulin signaling pathway, particularly the DAF-2-AGE-1-AKT-1/2-DAF-16 cascade in the intestine, is crucial for controlling GO toxicity on longevity.
• GO disrupts this pathway, leading to shortened lifespan, potentially through oxidative stress mechanisms regulated by DAF-16.
• These findings highlight the significant role of the insulin signaling pathway in mediating organismal responses to Graphene oxide exposure.