From molecular promise to preclinical results: HDAC inhibitors in the race for healthy aging drugs

Abstract Reversing or slowing the aging process brings great promise to treat or prevent age‐related disease, and targeting the hallmarks of aging is a strategy to achieve this. Epigenetics affects several if not all of the hallmarks of aging and has therefore emerged as a central target for interve...

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Main Authors: Rebecca L McIntyre, Eileen G Daniels, Marte Molenaars, Riekelt H Houtkooper, Georges E Janssens
Format: Article
Language:English
Published: Springer Nature 2019-08-01
Series:EMBO Molecular Medicine
Subjects:
Online Access:https://doi.org/10.15252/emmm.201809854
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author Rebecca L McIntyre
Eileen G Daniels
Marte Molenaars
Riekelt H Houtkooper
Georges E Janssens
author_facet Rebecca L McIntyre
Eileen G Daniels
Marte Molenaars
Riekelt H Houtkooper
Georges E Janssens
author_sort Rebecca L McIntyre
collection DOAJ
description Abstract Reversing or slowing the aging process brings great promise to treat or prevent age‐related disease, and targeting the hallmarks of aging is a strategy to achieve this. Epigenetics affects several if not all of the hallmarks of aging and has therefore emerged as a central target for intervention. One component of epigenetic regulation involves histone deacetylases (HDAC), which include the “classical” histone deacetylases (of class I, II, and IV) and sirtuin deacetylases (of class III). While targeting sirtuins for healthy aging has been extensively reviewed elsewhere, this review focuses on pharmacologically inhibiting the classical HDACs to promote health and longevity. We describe the theories of how classical HDAC inhibitors may operate to increase lifespan, supported by studies in model organisms. Furthermore, we explore potential mechanisms of how HDAC inhibitors may have such a strong grasp on health and longevity, summarizing their links to other hallmarks of aging. Finally, we show the wide range of age‐related preclinical disease models, ranging from neurodegeneration to heart disease, diabetes to sarcopenia, which show improvement upon HDAC inhibition.
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publishDate 2019-08-01
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spelling doaj-art-2b84af9709f4463188efcfc603c9e4eb2025-08-20T03:46:24ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842019-08-0111911110.15252/emmm.201809854From molecular promise to preclinical results: HDAC inhibitors in the race for healthy aging drugsRebecca L McIntyre0Eileen G Daniels1Marte Molenaars2Riekelt H Houtkooper3Georges E Janssens4Laboratory Genetic Metabolic Diseases, Amsterdam UMC, Amsterdam Gastroenterology and Metabolism, Amsterdam Cardiovascular Sciences, University of AmsterdamLaboratory Genetic Metabolic Diseases, Amsterdam UMC, Amsterdam Gastroenterology and Metabolism, Amsterdam Cardiovascular Sciences, University of AmsterdamLaboratory Genetic Metabolic Diseases, Amsterdam UMC, Amsterdam Gastroenterology and Metabolism, Amsterdam Cardiovascular Sciences, University of AmsterdamLaboratory Genetic Metabolic Diseases, Amsterdam UMC, Amsterdam Gastroenterology and Metabolism, Amsterdam Cardiovascular Sciences, University of AmsterdamLaboratory Genetic Metabolic Diseases, Amsterdam UMC, Amsterdam Gastroenterology and Metabolism, Amsterdam Cardiovascular Sciences, University of AmsterdamAbstract Reversing or slowing the aging process brings great promise to treat or prevent age‐related disease, and targeting the hallmarks of aging is a strategy to achieve this. Epigenetics affects several if not all of the hallmarks of aging and has therefore emerged as a central target for intervention. One component of epigenetic regulation involves histone deacetylases (HDAC), which include the “classical” histone deacetylases (of class I, II, and IV) and sirtuin deacetylases (of class III). While targeting sirtuins for healthy aging has been extensively reviewed elsewhere, this review focuses on pharmacologically inhibiting the classical HDACs to promote health and longevity. We describe the theories of how classical HDAC inhibitors may operate to increase lifespan, supported by studies in model organisms. Furthermore, we explore potential mechanisms of how HDAC inhibitors may have such a strong grasp on health and longevity, summarizing their links to other hallmarks of aging. Finally, we show the wide range of age‐related preclinical disease models, ranging from neurodegeneration to heart disease, diabetes to sarcopenia, which show improvement upon HDAC inhibition.https://doi.org/10.15252/emmm.201809854epigeneticsgeroprotectorhallmarks of agingHDAC inhibitorspreclinical models
spellingShingle Rebecca L McIntyre
Eileen G Daniels
Marte Molenaars
Riekelt H Houtkooper
Georges E Janssens
From molecular promise to preclinical results: HDAC inhibitors in the race for healthy aging drugs
EMBO Molecular Medicine
epigenetics
geroprotector
hallmarks of aging
HDAC inhibitors
preclinical models
title From molecular promise to preclinical results: HDAC inhibitors in the race for healthy aging drugs
title_full From molecular promise to preclinical results: HDAC inhibitors in the race for healthy aging drugs
title_fullStr From molecular promise to preclinical results: HDAC inhibitors in the race for healthy aging drugs
title_full_unstemmed From molecular promise to preclinical results: HDAC inhibitors in the race for healthy aging drugs
title_short From molecular promise to preclinical results: HDAC inhibitors in the race for healthy aging drugs
title_sort from molecular promise to preclinical results hdac inhibitors in the race for healthy aging drugs
topic epigenetics
geroprotector
hallmarks of aging
HDAC inhibitors
preclinical models
url https://doi.org/10.15252/emmm.201809854
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