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The Goals for Stem Cell Medicine Ultimately Include Repair of Aging

The long term goals for the field of stem cell medicine tend to come back around to include rejuvenation at some point. It's unavoidable, really: the medical conditions most obviously suited to treatment via stem cell therapies are the malfunctions and disrepair of old age - failing muscles, hearts, livers, and other more complex organs. But stem cell populations and their supporting infrastructure in the body also fail right at the time when they are most needed. (That progressive failure of stem cell capacity with age goes some way to causing the time of greatest need, of course, but it's far from the whole story of degenerative aging). The bottom line is that to ensure effectiveness for stem cell treatments in the old, efforts must be made to reverse the aging of their stem cells and the aging of stem cell support systems in the body.

You might recall the research group that demonstrated reversal of some aspects of stem cell aging in mice by introducing young blood into old animals - and vice versa, illustrating that the changes of aging observed in stem cells are due at least as much the environment within the body as to the cells themselves. Those scientists been working on the aging of stem cells for some years now, tracing mechanisms and looking for key biochemical switches; here is a piece that outlines their view of the future:

Unlike stem cells in the blood or skin, muscle stem cells spend most of their lives nestled in the surrounding tissue. "They don't do much most of the time," said Rando. "They remain in a quiescent state for most of a person's life. When you injure your muscle, however, they begin dividing to repair the damage. ... Although on the surface the quiescent state seems to be relatively static, it's quite actively maintained. We've found that changing the levels of just one specific microRNA in resting muscle stem cells, however, causes them to spring into action."

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If you're going to use muscle stem cells as a therapy for disease or aging, you want to be able to transplant cells that have the greatest potential to make new muscle in the recipient. The quiescent state most closely resembles how they are in the body. If you allow them to divide in the lab before transplantation, they are not as effective. This microRNA may allow us to toggle the cells back and forth between the actively dividing and quiescent states.

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In the future, the researchers will continue to look at the unique features of quiescent muscle stem cells, including those involved in normal aging. "We'd like to understand the aging process at a very fundamental level," said Rando. "That will allow us to move toward more therapeutic applications. Can we use what we've learned to convert old stem cells, which seem to have lost their responsiveness to activation cues, into young stem cells? Maybe the ability of old stem cells to exit the quiescent state is defective. We may one day be able to develop approaches that enhance tissue repair by enhancing stem cell function."

Paired with increasingly effective early detection and elimination of cancer, it should be very feasible in the years ahead to postpone the decline of stem cells in the body. That decline appears to exist as a mechanism to reduce the risk of cancer, but if cancer as a worrying condition becomes a thing of the past there's no reason for us not to dial our stem cells back up to full potency to maintain our tissues better and for longer.

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