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| Status |
Public on May 03, 2016 |
| Title |
Two Conserved Histone Demethylases Regulate Mitochondrial Stress-Induced Longevity |
| Organism |
Caenorhabditis elegans |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Across eukaryotic species, mild mitochondrial stress can have beneficial effects on the lifespan of organisms. Mitochondrial dysfunction activates an unfolded protein response (UPRmt), a stress signaling mechanism designed to ensure mitochondrial homeostasis. Perturbation of mitochondria during larval development in C. elegans not only delays aging but also maintains UPRmt signaling, suggesting an epigenetic mechanism that modulates both longevity and mitochondrial proteostasis throughout life. Here we identify the conserved histone lysine demethylases jmjd-1.2/PHF8 and jmjd-3.1/JMJD3 as positive regulators of lifespan in response to mitochondrial dysfunction across species. Reduction-of-function of the demethylases potently suppresses longevity and UPRmt induction while gain-of-function is sufficient to extend lifespan in an UPRmt-dependent manner. A systems genetics approach in the BXD mouse reference population further indicated conserved roles of the mammalian orthologs in longevity and UPRmt signaling. These findings illustrate an evolutionary conserved epigenetic mechanism that determines the rate of aging downstream of mitochondrial perturbations.
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| Overall design |
Comparison of gene expression changes in response to cco-1 RNAi treatment, overexpression of jmjd-1.2 and overexpression of jmjd-3.1 in populations of C. elegans L4 animals
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| |
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| Contributor(s) |
Steffen KK, Merkwirth C, Dillin A |
| Citation(s) |
27133168 |
| |
| Submission date |
Mar 08, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Andrew Dillin |
| E-mail(s) |
dillin@berkeley.edu
|
| Organization name |
University of California, Berkeley
|
| Lab |
Dillin Lab, 430E Li Ka Shing
|
| Street address |
188 Li Ka Shing
|
| City |
Berkeley |
| State/province |
CA |
| ZIP/Postal code |
94720 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL18245 |
Illumina HiSeq 2500 (Caenorhabditis elegans) |
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| Samples (15)
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| Relations |
| BioProject |
PRJNA314583 |
| SRA |
SRP071287 |
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