Inactivating histone deacetylase HDA promotes longevity by mobilizing trehalose metabolism
Autor: | Ruofan Yu, Jun-yi Zhu, Wei Liu, Weiwei Dang, Brian M. Wasko, Haiying Liu, Lidong Qin, Luyang Sun, Zhe Han, Xiaohua Cao, Matt Kaeberlein, Emeline Crutcher, Myeong Chan Jo |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Aging Saccharomyces cerevisiae Proteins DNA damage Science Longevity General Physics and Astronomy Repressor Saccharomyces cerevisiae Histone Deacetylases Article General Biochemistry Genetics and Molecular Biology Stress signalling 03 medical and health sciences Longevity Pathway chemistry.chemical_compound 0302 clinical medicine Animals Epigenetics Caenorhabditis elegans Multidisciplinary biology Trehalose Acetylation General Chemistry Cell biology Enzyme Activation Ageing Drosophila melanogaster 030104 developmental biology Histone chemistry biology.protein Histone deacetylase 030217 neurology & neurosurgery |
Zdroj: | Nature Communications Nature Communications, Vol 12, Iss 1, Pp 1-16 (2021) |
ISSN: | 2041-1723 |
Popis: | Histone acetylations are important epigenetic markers for transcriptional activation in response to metabolic changes and various stresses. Using the high-throughput SEquencing-Based Yeast replicative Lifespan screen method and the yeast knockout collection, we demonstrate that the HDA complex, a class-II histone deacetylase (HDAC), regulates aging through its target of acetylated H3K18 at storage carbohydrate genes. We find that, in addition to longer lifespan, disruption of HDA results in resistance to DNA damage and osmotic stresses. We show that these effects are due to increased promoter H3K18 acetylation and transcriptional activation in the trehalose metabolic pathway in the absence of HDA. Furthermore, we determine that the longevity effect of HDA is independent of the Cyc8-Tup1 repressor complex known to interact with HDA and coordinate transcriptional repression. Silencing the HDA homologs in C. elegans and Drosophila increases their lifespan and delays aging-associated physical declines in adult flies. Hence, we demonstrate that this HDAC controls an evolutionarily conserved longevity pathway. Histone acetylations are important epigenetic marks for transcriptional activation and respond to metabolic changes. Here the authors develop a lifespan screen and show that inactivation of the histone deacetylase complex activates longevity and protects against stress via trehalose metabolism. |
Databáze: | OpenAIRE |
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