Journal
AGING CELL
Volume 18, Issue 5, Pages -Publisher
WILEY
DOI: 10.1111/acel.12996
Keywords
aging; enhancer; extracellular matrix; JQ1; satellite cell; skeletal muscle
Categories
Funding
- General Research Funds (GRF) from the Research Grants Council (RGC) of the Hong Kong Special Administrative Region [14100415, 14133016, 14106117, 14100018, 14102315, 14116918, N_CUHK413/18]
- CUHK [1907307, 2017.049, 2017.009]
- National Natural Science Foundation (NSFC) of China [31871304]
Ask authors/readers for more resources
Epigenetic alterations occur in various cells and tissues during aging, but it is not known if such alterations are also associated with aging in skeletal muscle. Here, we examined the changes of a panel of histone modifications and found H3K27ac (an active enhancer mark) is markedly increased in aged human skeletal muscle tissues. Further analyses uncovered that the H3K27ac increase and enhancer activation are associated with the up-regulation of extracellular matrix (ECM) genes; this may result in alteration of the niche environment for skeletal muscle stem cells, also called satellite cells (SCs), which causes decreased myogenic potential and fibrogenic conversion of SCs. In mice, treatment of aging muscles with JQ1, an inhibitor of enhancer activation, inhibited the ECM up-regulation and fibrogenic conversion of SCs and restored their myogenic differentiation potential. Altogether, our findings not only uncovered a novel aspect of skeletal muscle aging that is associated with enhancer remodeling but also implicated JQ1 as a potential treatment approach for restoring SC function in aging muscle.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available