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Aging Triggers H3K27 Trimethylation Hoarding in the Chromatin of Nothobranchius furzeri Skeletal Muscle

Authors
  • Cencioni, Chiara
  • Heid, Johanna1
  • Krepelova, Anna2
  • Rasa, Seyed Mohammad Mahdi2
  • Kuenne, Carsten3
  • Guenther, Stefan3
  • Baumgart, Mario2
  • Cellerino, Alessandro
  • Neri, Francesco2
  • Spallotta, Francesco
  • Gaetano, Carlo
  • 1 Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA
  • 2 (F.N.)
  • 3 (S.G.)
Type
Published Article
Journal
Cells
Publisher
MDPI AG
Publication Date
Sep 28, 2019
Volume
8
Issue
10
Identifiers
DOI: 10.3390/cells8101169
PMID: 31569376
PMCID: PMC6829443
Source
PubMed Central
Keywords
License
Green

Abstract

Aging associates with progressive loss of skeletal muscle function, sometimes leading to sarcopenia, a process characterized by impaired mobility and weakening of muscle strength. Since aging associates with profound epigenetic changes, epigenetic landscape alteration analysis in the skeletal muscle promises to highlight molecular mechanisms of age-associated alteration in skeletal muscle. This study was conducted exploiting the short-lived turquoise killifish Nothobranchius furzeri ( Nfu ), a relatively new model for aging studies. The epigenetic analysis suggested a less accessible and more condensed chromatin in old Nfu skeletal muscle. Specifically, an accumulation of heterochromatin regions was observed as a consequence of increased levels of H3K27me3, HP1α, polycomb complex subunits, and senescence-associated heterochromatic foci (SAHFs). Consistently, euchromatin histone marks, including H3K9ac, were significantly reduced. In this context, integrated bioinformatics analysis of RNASeq and ChIPSeq, related to skeletal muscle of Nfu at different ages, revealed a down-modulation of genes involved in cell cycle, differentiation, and DNA repair and an up-regulation of inflammation and senescence genes. Undoubtedly, more studies are needed to disclose the detailed mechanisms; however, our approach enlightened unprecedented features of Nfu skeletal muscle aging, potentially associated with swimming impairment and reduced mobility typical of old Nfu .

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