HDAC2 and 7 down-regulation induces senescence in dermal fibroblasts

Céline Warnon, Karim Bouhjar, Noëlle Ninane, Mathilde Verhoyen, Antoine Fattaccioli, Maude Fransolet, Catherine Lambert de Rouvroit, Yves Poumay, Géraldine Piel, Denis Mottet, Florence Debacq-Chainiaux

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)17978-18005
Number of pages28
JournalAging
Volume13
Issue number14
DOIs
Publication statusPublished - 31 Jul 2021

Keywords

  • fibroblasts
  • histone deacetylases
  • SAHA
  • SASP
  • senescence

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