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Research Paper|Volume 13, Issue 14|pp 17978—18005

HDAC2 and 7 down-regulation induces senescence in dermal fibroblasts

Céline Warnon1, Karim Bouhjar1, Noëlle Ninane1, Mathilde Verhoyen1, Antoine Fattaccioli1, Maude Fransolet1, Catherine Lambert de Rouvroit2, Yves Poumay2, Géraldine Piel3, Denis Mottet4, Florence Debacq-Chainiaux1
  • 1URBC, Namur Research Institute for Life Sciences (NARILIS), University of Namur, Namur, Belgium
  • 2URPHYM, Namur Research Institute for Life Sciences (NARILIS), University of Namur, Namur, Belgium
  • 3Laboratory of Pharmaceutical Technology and Biopharmacy, CIRM, University of Liège, Liège, Belgium
  • 4University of Liège, GIGA-Molecular Biology of Diseases, Gene Expression and Cancer Laboratory, Liège, Belgium
Received: February 22, 2021Accepted: July 2, 2021Published: July 12, 2021
https://doi.org/10.18632/aging.203304

Copyright: © 2021 Warnon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Originally simply reported to be in a stable and irreversible growth arrest in vitro, senescent cells are now clearly associated with normal and pathological ageing in vivo. They are characterized by several biomarkers and changes in gene expression that may depend on epigenetic factors, such as histone acetylation, involving a balance between histone acetyltransferases (HATs) and histone deacetylases (HDACs). In this study, we investigate the expression and the role of HDACs on the senescent phenotype of dermal fibroblasts. We report that during replicative senescence, most canonical HDACs are less expressed. Moreover, treatment with SAHA, a histone deacetylase inhibitor (HDACi) also known as Vorinostat, or the specific downregulation of HDAC2 or HDAC7 by siRNA, induces the appearance of senescence biomarkers of dermal fibroblasts. Conversely, the ectopic re-expression of HDAC7 by lentiviral transduction in pre-senescent dermal fibroblasts extends their proliferative lifespan. These results demonstrate that HDACs expression can modulate the senescent phenotype, highlighting their pharmaceutical interest in the context of healthy ageing.