Targeting Gene Expression To Prevent Age-Related Muscle Loss

• Sarcopenia is the progressive loss of muscle mass with age, thought to be caused by the decline of the stem cells responsible for repairing damaged muscle.
• Researchers studied changes in the muscle stem cells of ageing mice. They observed changes in the way the DNA of older stem cells was packaged, which reduced their ability to produce muscle repair proteins.
• Researchers were able to restore stem cell function by targeting a specific transcription factor – a molecule that controls gene expression.

Sarcopenia is a progressive loss of muscle mass that occurs with age, and appears to be primarily caused by the decline and death of muscle stem cells: the cells responsible for repairing damaged muscle tissue. But what causes these cells to stop functioning? Answering that question may be the key to reversing this process.

Our muscles start to shrink and weaken when we reach our 50s and 60s in a process called sarcopenia, but new research in mice from the University of Michigan offers new insights into why this loss may occur, and how we might begin to prevent it.

Researchers used bioinformatics analysis to observe how older muscle stem cells lose the packaging, or chromatin, of DNA in the nucleus of stem cells. The authors observed changes in the way chromatin opened and exposed sites of DNA in aging. The changes in accessibility of chromatin rendered differences in the way DNA binding proteins (transcription factors) acted, specifically at genes that make proteins for repairing muscle injuries. The researchers discovered how one transcription factor has the ability to block the protein binding action of others.

The researchers were then able to target this transcription factor to restore function to muscle stem cells. Research lead Carlos Aguilar explains:

“By silencing the activity of that one transcription factor, we were able to restore the ability of these older stem cells to fuse and build tissue again, as in youth. The opening and closing of the chromatin packaging is an elegant system stem cells use to maintain themselves, respond to injury or repair tissue.

“As that chromatin layer changes with age, the ability of stem cells to execute their functions is weakened. Our group is trying to understand and engineer this layer on top of the genome to prevent the loss of stem cells and their function, and extend their healthy lifespan.”

Click here to view original web page at phys.org

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