| Autor: |
Shruthi Hamsanathan, Tamil Anthonymuthu, Suhao Han, Himaly Shinglot, Ella Siefken, Austin Sims, Payel Sen, Hannah L. Pepper, Nathaniel W. Snyder, Hulya Bayir, Valerian Kagan, Aditi U. Gurkar |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Science advances. 8(7) |
| ISSN: |
2375-2548 |
| Popis: |
Although DNA damage is intricately linked to metabolism, the metabolic alterations that occur in response to DNA damage are not well understood. We use a DNA repair–deficient model of ERCC1-XPF in Caenorhabditis elegans to gain insights on how genotoxic stress drives aging. Using multi-omic approach, we discover that nuclear DNA damage promotes mitochondrial β-oxidation and drives a global loss of fat depots. This metabolic shift to β-oxidation generates acetyl–coenzyme A to promote histone hyperacetylation and an associated change in expression of immune-effector and cytochrome genes. We identify the histone acetyltransferase MYS-1, as a critical regulator of this metabolic-epigenetic axis. We show that in response to DNA damage, polyunsaturated fatty acids, especially arachidonic acid (AA) and AA-related lipid mediators, are elevated and this is dependent on mys-1 . Together, these findings reveal that DNA damage alters the metabolic-epigenetic axis to drive an immune-like response that can promote age-associated decline. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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