Increased alcohol dehydrogenase 1 activity promotes longevity.

Autor:	Ghaddar A; Department of Biology, College of Arts and Sciences, University of Virginia, Charlottesville, VA 22903, USA., Mony VK; Department of Biology, College of Arts and Sciences, University of Virginia, Charlottesville, VA 22903, USA., Mishra S; Department of Biology, College of Arts and Sciences, University of Virginia, Charlottesville, VA 22903, USA; Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22903, USA., Berhanu S; Department of Biology, College of Arts and Sciences, University of Virginia, Charlottesville, VA 22903, USA., Johnson JC; Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22903, USA., Enriquez-Hesles E; Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22903, USA., Harrison E; Department of Biology, College of Arts and Sciences, University of Virginia, Charlottesville, VA 22903, USA., Patel A; Department of Biology, College of Arts and Sciences, University of Virginia, Charlottesville, VA 22903, USA., Horak MK; Department of Biology, College of Arts and Sciences, University of Virginia, Charlottesville, VA 22903, USA; Department of Cell Biology, School of Medicine, University of Virginia, Charlottesville, VA 22903, USA., Smith JS; Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22903, USA., O'Rourke EJ; Department of Biology, College of Arts and Sciences, University of Virginia, Charlottesville, VA 22903, USA; Department of Cell Biology, School of Medicine, University of Virginia, Charlottesville, VA 22903, USA; Robert M. Berne Cardiovascular Research Center, School of Medicine, University of Virginia, Charlottesville, VA 22903, USA. Electronic address: ejorourke@virginia.edu.
Jazyk:	angličtina
Zdroj:	Current biology : CB [Curr Biol] 2023 Mar 27; Vol. 33 (6), pp. 1036-1046.e6. Date of Electronic Publication: 2023 Feb 17.
DOI:	10.1016/j.cub.2023.01.059
Abstrakt:	Several molecules can extend healthspan and lifespan across organisms. However, most are upstream signaling hubs or transcription factors orchestrating complex anti-aging programs. Therefore, these molecules point to but do not reveal the fundamental mechanisms driving longevity. Instead, downstream effectors that are necessary and sufficient to promote longevity across conditions or organisms may reveal the fundamental anti-aging drivers. Toward this goal, we searched for effectors acting downstream of the transcription factor EB (TFEB), known as HLH-30 in C. elegans, because TFEB/HLH-30 is necessary across anti-aging interventions and its overexpression is sufficient to extend C. elegans lifespan and reduce biomarkers of aging in mammals including humans. As a result, we present an alcohol-dehydrogenase-mediated anti-aging response (AMAR) that is essential for C. elegans longevity driven by HLH-30 overexpression, caloric restriction, mTOR inhibition, and insulin-signaling deficiency. The sole overexpression of ADH-1 is sufficient to activate AMAR, which extends healthspan and lifespan by reducing the levels of glycerol-an age-associated and aging-promoting alcohol. Adh1 overexpression is also sufficient to promote longevity in yeast, and adh-1 orthologs are induced in calorically restricted mice and humans, hinting at ADH-1 acting as an anti-aging effector across phyla. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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