| Autor: |
Ursula Jakob, Bryndon Oleson, Janakraj Bhattrai, Sarah Zalubas, Tessa Kravchenko, Yuanyuan Ji, Emily Jiang, Christine Lu, Ciara Madden, Daphne Bazopoulou, Jace Jones |
| Rok vydání: |
2023 |
| DOI: |
10.21203/rs.3.rs-2782739/v1 |
| Popis: |
Recent studies revealed that early-in-life events can have highly beneficial long-term effects in animals. We now demonstrate that exposure of Caenorhabditis elegans to reactive oxygen species during development protects against amyloid-induced proteotoxicity later in life. We show that this protection is initiated by the inactivation of the redox sensitive H3K4me3 modifying COMPASS complex, and conferred by a substantial increase in the heat shock independent activity of heat shock factor 1 (HSF-1), a longevity factor known to act predominantly during C. elegans development. We show that depletion of HSF-1 leads to dramatic rearrangements of the organismal lipid landscape, and a significant decrease in mitochondrial β-oxidation. Both of these activities appear to majorly contribute to HSF-1’s protective effects against amyloid toxicity. In summary, our study reveals previously unknown links between developmental changes in the histone landscape, HSF-1 activity and lipid metabolism and the protection against age-associated amyloid toxicities later in life. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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