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HIGH THROUGHPUT YEAST REPLICATIVE LIFESPAN SCREEN UNCOVERS HISTONE DEACETYLASE HDA AS NOVEL REGULATOR OF AGING

In this work, we set out to develop a high throughput screening method, SEBYL (SEquencing Based Yeast replicative Lifespan screen), in order to identify new aging regulators in budding yeast. By utilizing SEBYL on yeast knockout collection, we were able to identify 285 long-lived gene deletions, of...

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Detalles Bibliográficos
Autores principales: Yu, Ruofan, Cao, Xiaohua, Dang, Weiwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844737/
http://dx.doi.org/10.1093/geroni/igz038.3210
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author Yu, Ruofan
Cao, Xiaohua
Dang, Weiwei
author_facet Yu, Ruofan
Cao, Xiaohua
Dang, Weiwei
author_sort Yu, Ruofan
collection PubMed
description In this work, we set out to develop a high throughput screening method, SEBYL (SEquencing Based Yeast replicative Lifespan screen), in order to identify new aging regulators in budding yeast. By utilizing SEBYL on yeast knockout collection, we were able to identify 285 long-lived gene deletions, of which a significant portion was proven to have extended lifespan by previous classical experiments. To demonstrate the ability of our method to discover new genes and pathways involved in aging process, we focused on characterizing one newly identified long-lived candidate emerged from the screening, histone deacetylase complex HDA, and found it regulates aging through mediating stress response pathways, especially DNA damage stress response. Presence of HDA complex inhibits expression of trehalose metabolism genes, which act as stress protectant. When HDA complex is mutated, trehalose genes are de-repressed, enhancing stress response and eventually promotes longevity. In summary, we conclude SEBYL to be time and energy saving, robust, and suitable for discovery of aging regulating genes using various preexisting yeast mutant collection resource.
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spelling pubmed-68447372019-11-18 HIGH THROUGHPUT YEAST REPLICATIVE LIFESPAN SCREEN UNCOVERS HISTONE DEACETYLASE HDA AS NOVEL REGULATOR OF AGING Yu, Ruofan Cao, Xiaohua Dang, Weiwei Innov Aging Session Lb1545 (Late Breaking Poster) In this work, we set out to develop a high throughput screening method, SEBYL (SEquencing Based Yeast replicative Lifespan screen), in order to identify new aging regulators in budding yeast. By utilizing SEBYL on yeast knockout collection, we were able to identify 285 long-lived gene deletions, of which a significant portion was proven to have extended lifespan by previous classical experiments. To demonstrate the ability of our method to discover new genes and pathways involved in aging process, we focused on characterizing one newly identified long-lived candidate emerged from the screening, histone deacetylase complex HDA, and found it regulates aging through mediating stress response pathways, especially DNA damage stress response. Presence of HDA complex inhibits expression of trehalose metabolism genes, which act as stress protectant. When HDA complex is mutated, trehalose genes are de-repressed, enhancing stress response and eventually promotes longevity. In summary, we conclude SEBYL to be time and energy saving, robust, and suitable for discovery of aging regulating genes using various preexisting yeast mutant collection resource. Oxford University Press 2019-11-08 /pmc/articles/PMC6844737/ http://dx.doi.org/10.1093/geroni/igz038.3210 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Session Lb1545 (Late Breaking Poster)
Yu, Ruofan
Cao, Xiaohua
Dang, Weiwei
HIGH THROUGHPUT YEAST REPLICATIVE LIFESPAN SCREEN UNCOVERS HISTONE DEACETYLASE HDA AS NOVEL REGULATOR OF AGING
title HIGH THROUGHPUT YEAST REPLICATIVE LIFESPAN SCREEN UNCOVERS HISTONE DEACETYLASE HDA AS NOVEL REGULATOR OF AGING
title_full HIGH THROUGHPUT YEAST REPLICATIVE LIFESPAN SCREEN UNCOVERS HISTONE DEACETYLASE HDA AS NOVEL REGULATOR OF AGING
title_fullStr HIGH THROUGHPUT YEAST REPLICATIVE LIFESPAN SCREEN UNCOVERS HISTONE DEACETYLASE HDA AS NOVEL REGULATOR OF AGING
title_full_unstemmed HIGH THROUGHPUT YEAST REPLICATIVE LIFESPAN SCREEN UNCOVERS HISTONE DEACETYLASE HDA AS NOVEL REGULATOR OF AGING
title_short HIGH THROUGHPUT YEAST REPLICATIVE LIFESPAN SCREEN UNCOVERS HISTONE DEACETYLASE HDA AS NOVEL REGULATOR OF AGING
title_sort high throughput yeast replicative lifespan screen uncovers histone deacetylase hda as novel regulator of aging
topic Session Lb1545 (Late Breaking Poster)
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844737/
http://dx.doi.org/10.1093/geroni/igz038.3210
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