Targeting epigenetic mechanisms in progenitor cells for functional rejuvenation of whole organs
Epigenetic alterations are a hallmark of aging, affecting DNA and histone modifications, 3D genome structure, and gene expression. Dr. Sen's lab studies these changes in various tissues to understand their unique and shared characteristics. In this project, Dr. Sen's team will focus on the skeletal muscle, which makes up ~40% of the body weight, contributes to ~30% of resting energy expenditure, and is affected by aging. Aging reduces muscle mass and strength, partly due to the reduced function of resident muscle stem cells (MuSCs). The team used an integrative multi-omics approach to profile the transcriptome, epigenome, and 3D genome of MuSCs isolated from young, old, and geriatric mice and comprehensively understand why their regenerative potential diminishes with age. They found an elevated immune response and quiescence exit signature in MuSCs during aging and identified regulatory elements that contribute to these changes. Targeting these networks can potentially rejuvenate MuSC function.
