Inactivating histone deacetylase HDA promotes longevity by mobilizing trehalose metabolism
Wasko, Brian M
Jo, Myeong Chan
PublisherNature Publishing Group
MetadataShow full item record
AbstractHistone 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.
Identifier to cite or link to this itemhttp://hdl.handle.net/10713/15409
- Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila.
- Authors: Burnett C, Valentini S, Cabreiro F, Goss M, Somogyvári M, Piper MD, Hoddinott M, Sutphin GL, Leko V, McElwee JJ, Vazquez-Manrique RP, Orfila AM, Ackerman D, Au C, Vinti G, Riesen M, Howard K, Neri C, Bedalov A, Kaeberlein M, Soti C, Partridge L, Gems D
- Issue date: 2011 Sep 21
- Ageing. Yeast longevity gene goes public.
- Authors: Gems D
- Issue date: 2001 Mar 8
- Histone deacetylase HDA-1 modulates mitochondrial stress response and longevity.
- Authors: Shao LW, Peng Q, Dong M, Gao K, Li Y, Li Y, Li CY, Liu Y
- Issue date: 2020 Sep 15
- Caenorhabditis elegans histone deacetylase hda-1 is required for morphogenesis of the vulva and LIN-12/Notch-mediated specification of uterine cell fates.
- Authors: Ranawade AV, Cumbo P, Gupta BP
- Issue date: 2013 Aug 7
- Mutation in histone deacetylase HDA-3 leads to shortened locomotor healthspan in <i>Caenorhabditis elegans</i>.
- Authors: Kawamura K, Maruyama IN
- Issue date: 2020 Dec 3