Epigenetic regulation of fat metabolism and longevity in C. elegans
Abstract/Contents
- Abstract
- Chromatin and metabolic states both influence lifespan, but how they interact in lifespan regulation is largely unknown. The COMPASS chromatin complex, which trimethylates lysine 4 on histone H3 (H3K4me3), regulates lifespan in C. elegans. However, the mechanism by which H3K4me3 modifiers impact longevity, and whether it involves metabolic changes, remains unclear. Here we find that H3K4me3- methyltransferase deficiency, which extends lifespan, promotes fat accumulation with a specific enrichment of mono-unsaturated fatty acids (MUFAs). This fat metabolism switch in H3K4me3-methyltransferase deficient animals is mediated at least in part by downregulation of germline targets, including S6 kinase, and by activation of an intestinal transcriptional network that upregulates delta-9 fatty acid desaturases. Interestingly, MUFA accumulation is necessary for the lifespan extension of H3K4me3-methyltransferase deficient worms, and dietary MUFAs are sufficient to extend lifespan. Given the conservation of lipid metabolism, dietary or endogenous MUFAs could extend lifespan and healthspan in other species, including mammals.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2017 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Han, Shuo |
|---|---|
| Associated with | Stanford University, Program in Genetics. |
| Primary advisor | Brunet, Anne, 1972- |
| Thesis advisor | Brunet, Anne, 1972- |
| Thesis advisor | Fire, Andrew Zachary |
| Thesis advisor | Gozani, Or Pinchas |
| Thesis advisor | Kim, Stuart |
| Advisor | Fire, Andrew Zachary |
| Advisor | Gozani, Or Pinchas |
| Advisor | Kim, Stuart |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Shuo Han. |
|---|---|
| Note | Submitted to the Program in Genetics. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2017. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2017 by Shuo Han
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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