A fasting-responsive signaling pathway that extends life span in C. elegans.

Area of Science:

• Cellular Biology
• Genetics
• Aging Research

Background:

• Intermittent fasting (IF) is a dietary strategy shown to extend lifespan in various organisms.
• The precise molecular mechanisms sensing and responding to fasting stimuli for longevity remain largely unidentified.
• Key longevity pathways often involve transcription factors like FOXO, but other signaling routes are under investigation.

Purpose of the Study:

• To elucidate the molecular mechanisms underlying fasting-induced longevity in C. elegans.
• To identify novel signaling pathways involved in sensing and transducing the fasting stimulus.
• To understand the role of transcription factors beyond DAF-16 in fasting responses.

Main Methods:

• Comprehensive transcriptome analysis in C. elegans under fasting conditions.
• Investigating the role of KGB-1 (a JNK) and AP-1 (JUN-1/FOS-1) in fasting response.
• Assessing the impact of KGB-1 and AP-1 on longevity and proteostasis markers.

Main Results:

• AP-1 (JUN-1/FOS-1) was identified as a crucial transcription factor in fasting-induced gene expression changes, alongside DAF-16.
• The JNK KGB-1 acts as an activator of AP-1 and is upregulated by fasting.
• The KGB-1/AP-1 pathway, along with DAF-16, upregulates SCF E3 ubiquitin ligase components, enhancing protein ubiquitination and reducing carbonylation.

Conclusions:

• A novel fasting-responsive signaling pathway involving KGB-1 and AP-1 was identified.
• This pathway, in conjunction with DAF-16, mediates intermittent fasting-induced longevity.
• The mechanism involves transcriptional regulation of proteostasis, including protein ubiquitination and carbonylation reduction.