Thursday, June 27, 2013

Young stem cells’ DNA has more genes switched to "on" position than geriatric ones

Skeletal muscle courtesy of Wikimedia Commons
Researchers at Stanford University have made a start in understanding why muscles in younger people heal so quickly compared to muscles in older people. Understanding these differences could help scientists find ways of helping muscles in older people heal more quickly after injuries.

In a study comparing muscle stem cells from young and old mice, the group found that histones, proteins that are intimately wound up with the DNA of animal and plant cells, display different chemical properties depending on how old the mice are. These changes seem to directly relate to why the older muscle stem cells don’t respond as promptly to injured muscle.

A few years ago, the team, led by Thomas Rando, realized that muscle cells of older mice exposed to a young mouse’s blood regained the capacity to heal themselves. They took a closer look at what caused this rejuvenation, suspecting histones were involved.

In cells that have a nucleus, the long strands of DNA wrap themselves around small bead-like histone proteins. This helps keep the DNA stored neatly. Histones also act like switches to turn genes on or off. Every cell in a human body has nearly identical genetic information, but histones are one reason brain cells only express brain cell genes, blood cells only express blood cell genes and muscle cells only express muscle cell genes.

The study describes the team’s recent work with satellite cells, a rare kind of adult stem cell . They usually lay dormant, but pop into action when a muscle is injured to repair it by replacing muscle cells. When they looked at histones from dormant satellite cells of young mice and old mice side-by-side, the researchers were surprised to find that young-mouse satellite cells had histones with the “on” signal switched on not just for muscle cells, but also for several other cell types.

In a press release, about the findings, Rando said,
“When you look at these satellite cells the way we did, they seem ready to become all kinds of cells. It’s a mystery,” he said, suggesting that it could mean stem cells thought to be committed to a particular lineage may be capable of becoming other types of tissue entirely.

“Maybe their fates are not permanently sealed,” he said. “The door is not locked. Who knows what could happen if they’re given the right signals?”
The study was published today in the journal Cell Reports.

The team is now looking more closely at which histone changes are reversible in aging cells and testing other types of adult stem cells for this property. A former member of Rando’s lab, Irena Conboy at UC Berkeley, is also investigating the differences between old and young tissues to develop therapies for muscle injuries or diseases like muscular dystrophies. There’s more information about this CIRM-funded project on our web page.

R.S.L.

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