TY - JOUR
T1 - Aging Triggers H3K27 Trimethylation Hoarding in the Chromatin of Nothobranchius furzeri Skeletal Muscle.
AU - Cencioni, Chiara
AU - Heid, Johanna
AU - Krepelova, Anna
AU - Rasa, Seyed Mohammad Mahdi
AU - Kuenne, Carsten
AU - Guenther, Stefan
AU - Baumgart, Mario
AU - Cellerino, Alessandro
AU - Neri, Francesco
AU - Spallotta, Francesco
AU - Gaetano, Carlo
PY - 2019/9/1
Y1 - 2019/9/1
N2 - 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 .
AB - 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 .
KW - Nothobranchius furzeri
KW - aging
KW - chromatin
KW - epigenetic changes
KW - frailty
KW - histone modifications
KW - sarcopenia
KW - skeletal muscle
U2 - 10.3390/cells8101169
DO - 10.3390/cells8101169
M3 - Articolo
VL - 8
JO - Cells
JF - Cells
SN - 2073-4409
ER -