Enhancer Rewiring Orchestrates Inflammation And Loss Of Cell Identity During Muscle Stem Cell Aging
As we age, our bodies lose some of their ability to repair and regenerate tissues, and a key reason for this is the decline of our stem cells. This is particularly true for the stem cells in our skeletal muscles, called muscle stem cells (MuSCs), which become less effective over time, contributing to weaker muscles and slower recovery from injury.
Recent research has shed light on the molecular changes happening within these aging muscle stem cells. Scientists used advanced techniques to examine the entire genetic landscape, including how genes are turned on or off (the epigenome), which genes are active (the transcriptome), and even how the DNA is folded within the cell’s nucleus (the 3D genome) in mice of different ages and sexes.
The findings revealed that even in early stages of aging, especially in males, muscle stem cells start to show signs of increased inflammation and begin to lose their unique identity as muscle repair cells. As aging progresses, these cells exhibit even higher levels of inflammation, a widespread activation of “enhancers” (regions of DNA that act like switches to boost gene activity), and significant “3D genome rewiring,” meaning the intricate way DNA is organized inside the cell changes dramatically. These inflammatory processes are linked to specific signaling pathways in the body.
Ultimately, these progressive molecular shifts explain why muscle stem cells struggle to multiply and function correctly as we get older, contributing to the overall decline in muscle regeneration. Understanding these changes could pave the way for new strategies to maintain muscle health and regenerative capacity in an aging population.
Source: link to paper