Signalling through RHEB-1 mediates intermittent fasting-induced longevity in C. elegans

Area of Science:

• Aging and longevity research
• Molecular biology
• Genetics

Background:

• Dietary restriction, including intermittent fasting (IF), is a proven method to extend lifespan and reduce age-related diseases in various species.
• The molecular mechanisms driving IF-induced longevity are not fully understood.
• IF can increase lifespan without significant calorie reduction, highlighting unique pathways.

Purpose of the Study:

• To investigate the molecular mechanisms of intermittent fasting (IF)-induced longevity.
• To identify key proteins and pathways involved in IF's lifespan-extending effects.
• To establish an IF regimen in Caenorhabditis elegans and analyze its impact on gene expression.

Main Methods:

• Established an intermittent fasting (IF) regimen in Caenorhabditis elegans.
• Analyzed the role of the GTPase RHEB-1 in IF-induced lifespan extension.
• Investigated the interaction between RHEB-1, DAF-16, and the insulin/IGF signaling pathway.
• Examined gene expression changes associated with fasting and RHEB-1 function.

Main Results:

• Intermittent fasting (IF) significantly extends lifespan in C. elegans.
• The GTPase RHEB-1 plays a dual role: essential for IF longevity and mimicking caloric restriction when inhibited.
• RHEB-1 mediates IF effects partly through the insulin/IGF signaling effector DAF-16.
• Fasting-induced gene upregulation largely depends on RHEB-1; RHEB-1 and TOR signaling regulate fasting-induced downregulation of INS-7.

Conclusions:

• Signaling by RHEB-1 is crucial for IF-induced longevity and associated gene expression changes.
• A molecular link between IF-induced longevity and the insulin/IGF signaling pathway is established.
• RHEB-1 acts as a key regulator connecting fasting, gene expression, and lifespan extension.