Epigenetic mechanisms of muscle aging

National Institute On Aging

Investigators

Abstract

In the past year we have extensively analyzed multi-omic data such as RNA-seq, CUT&RUN, ATAC-seq, and Hi-C from young, old and geriatric mice. Our findings have revealed age-related differential gene expression in old and geriatric MuSCs with prominent upregulation of immune-related mRNAs and downregulation of a subset of collagen mRNAs. We further noted aged MuSCs accumulated active enhancers with enrichment in H3K27ac mark. We used a multi-omic integration tool to prioritize enhancers that are most active during aging and found potential regulatory activity at inflammatory and cell identity genes. We are now performing functional experiments to determine if histone acetyltransferase inhibitors can downregulate immune gene expression, ameliorate inflammation, reset cell identity, and improve regenerative capacity of the muscle in old mice.