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

Chiara Cencioni, Johanna Heid, Anna Krepelova, Seyed Mohammad Mahdi Rasa, Carsten Kuenne, Stefan Guenther, Mario Baumgart, Alessandro Cellerino, Francesco Neri, Francesco Spallotta, Carlo Gaetano

Research output: Contribution to journalArticlepeer-review

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 ( ), a relatively new model for aging studies. The epigenetic analysis suggested a less accessible and more condensed chromatin in old 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 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 skeletal muscle aging, potentially associated with swimming impairment and reduced mobility typical of old .
Original languageUndefined/Unknown
JournalCells
Volume8
DOIs
Publication statusPublished - Sep 1 2019

Keywords

  • Nothobranchius furzeri
  • aging
  • chromatin
  • epigenetic changes
  • frailty
  • histone modifications
  • sarcopenia
  • skeletal muscle

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