A fasting-responsive signaling pathway that extends life span in C. elegans
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
Abstract
Intermittent fasting is one of the most effective dietary restriction regimens that extend life span in C. elegans and mammals. Fasting-stimulus responses are key to the longevity response; however, the mechanisms that sense and transduce the fasting stimulus remain largely unknown. Through a comprehensive transcriptome analysis in C. elegans, we find that along with the FOXO transcription factor DAF-16, AP-1 (JUN-1/FOS-1) plays a central role in fasting-induced transcriptional changes. KGB-1, one of the C. elegans JNKs, acts as an activator of AP-1 and is activated in response to fasting. KGB-1 and AP-1 are involved in intermittent fasting-induced longevity. Fasting-induced upregulation of the components of the SCF E3 ubiquitin ligase complex via AP-1 and DAF-16 enhances protein ubiquitination and reduces protein carbonylation. Our results thus identify a fasting-responsive KGB-1/AP-1 signaling pathway, which, together with DAF-16, causes transcriptional changes that mediate longevity, partly through regulating proteostasis.
Details
Original language | English |
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Pages (from-to) | 79-91 |
Number of pages | 13 |
Journal | Cell reports |
Volume | 3 |
Issue number | 1 |
Publication status | Published - 31 Jan 2013 |
Peer-reviewed | Yes |
External IDs
Scopus | 84873121957 |
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Keywords
Keywords
- Animals, Caenorhabditis elegans/drug effects, Caenorhabditis elegans Proteins/metabolism, Fasting, Forkhead Transcription Factors, Gene Expression Profiling, Gene Expression Regulation/drug effects, JNK Mitogen-Activated Protein Kinases/metabolism, Longevity/drug effects, Signal Transduction/drug effects, Stem Cell Factor/metabolism, Transcription Factor AP-1/metabolism, Transcription Factors/metabolism, Transcription, Genetic/drug effects, Ubiquitin-Protein Ligases/metabolism, p38 Mitogen-Activated Protein Kinases/metabolism