iScience at the University of Hong Kong discovers changes in aging stem cells and how to reverse them

Aging and the struggle against it have been a hot theme
in both classical and modern literature throughout human history.
From the ill-fated Qin Shi Huang who went to sea in search of immortality, to the popularity of Count Dracula in the West, aging is a mystery that has captured the world's imagination for thousands of years but has not yet been solved
.

The research team led by Tom CHEUNG, associate professor of life sciences at the Hong Kong University of Science and Technology, which focuses on muscle stem cells (MuSCs), which play a key role in muscle repair, has discovered a method to identify aging muscle stem cells based on their chromatin characteristics, which is an exciting development
.

Unlike young muscle cells, senescent muscle cells exhibit weaker stem cell properties (the ability to become new stem cells or transform into specialized cells to replace damaged tissue).

If the chromatin profile of aging cells can be restored to that of young cells, then the process of cellular aging, in this case, the aging of skeletal muscle tissue, can be paused or even reversed
.
Their findings were recently published in iScience
, an open-access journal published by Cell Press.

"Regulation of chromatin accessibility is critical to the determination of cell fate, and changes in chromatin status can lead to dysregulated
gene expression.
In our study, we were able to determine that long-activated chromatin status is a hallmark of stem cell aging, which may be the goal of
developing anti-aging strategies.
”

Chromatin is a DNA complex that wraps around histones to maintain the normal structure of DNA, and its structure changes rapidly as the external environment changes
.
As a continuation of their previous research, the team prefixed muscle stem cells from mice to obtain quiescent cells (dormant cells that activate to repair injured muscles) and obtained their genetic and chromatin signatures, and then they compared chromatin accessibility over time
.

"We found that the chromatin environment of young muscle stem cells is very compact at rest, becomes highly accessible during early activation, and gradually re-establishes a compact state
after long-term regeneration.
However, senescent muscle stem cells lose their ability to
maintain this dense chromatin environment at rest.
”

Since scientists already have a better understanding of what happens to senescent cells, many possibilities are waiting to be explored, opening up multiple avenues
for further research into anti-aging strategies.

"Have we solved the mystery of aging? Yes, but not quite, if we can find chromatin modification regulators that are downregulated in senescent stem cells, these will be potential targets
for preventing aging by restoring their expression.
Since we were able to clearly compare the chromatin status of young and old muscle stem cells, we also identified specifically reachable target locations
in young muscle stem cells.
If we can maintain access to these areas during aging, we may find ways
to keep our cells younger and healthier.
”

"Our current study describes changes in chromatin accessibility during stem cell isolation and activation, but the journey is just beginning," Zhang said
.
"We look forward to further investigating the mechanisms that alter chromatin state during muscle stem cell isolation and activation, and it is important that we conduct the same studies in vivo to gain more insights
.
"

Original:

Global chromatin accessibility profiling analysis reveals a chronic activation state in aged muscle stem cells