How Reprogrammed Cells Gave Old Mice New Youth

Aging isn't a one-way street, finds a new study in which aged mice had their youthfulness restored.

Time only flows in one direction, but the same doesn't necessarily hold true for the aging process, finds a new study in which scientists successfully reprogrammed cells in mice in order to roll back the clock.

The new study, published in the journal Cell, found that through systemic cellular reprogramming scientists managed to extend the lives of mice carrying a mutation that predisposes them to premature aging, resulting in an average lifespan increase by around a third, from 18 weeks to 24.

"Previous studies from different laboratories including ours demonstrated that cellular reprogramming to pluripotency has the capacity to rejuvenate old cells in culture (in a dish) to a younger state," lead investigator Juan Carlos Izpisua Belmonte, professor in the Salk Institute of Biological Science's Gene Expression Laboratory, told Seeker. But the latest research marks the first cellular reprogramming has extended the life of a living organism.

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So what exactly does cellular reprogramming entail? At its most basic, the process involves converting one type of cell to another. For this study, adult cells, a skin cell or a blood cell, is converted into induced pluripotent stem cells, or iPSC.

"Cellular reprogramming is achieved through the expression of what are called the reprogramming factors or Yamanaka factors (Oct4, Sox2, Klf4 and c-Myc)." Izpisua Belmonte explained. "These factors are able to change the program of a cell and convert this cell into an iPSC."

"This conversion works through remodeling of the epigenome, through changes in the epigenetic marks in our genome," he said. "Coincidentally, these marks are also changed during aging, and that is why we can restore them back to a younger state using reprogramming."

Using this process just two days per week led to significant improvements in many organs, muscles and the cardiovascular system. In older mice, reprogramming improved the regenerative capacity of the pancreas and muscles after injury.

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While that's all well and good for mice, what about humans? Researchers are working on chemical and molecular means of inducing cellular reprogramming, Izpisua Belmonte reports. These could take the form of creams or injections to rejuvenate tissues, organs or bones, and clinical trials could take place in the next 10 years.

For now though, anyone searching for ways to reclaim their youth, the new study offers a glimmer of hope of a future when old age doesn't necessarily mean showing your years. Aging isn't a static, undirectional process, but plastic and dynamic.

"Aging is the major risk factor for most human disease and a major socioeconomical problem as modern societies get older, Izpisua Belmonte says. "Therefore, development of novel therapies that can slow down or reverse the aging process will have a major impact in many human diseases. Our goal is not only to extend lifespan, but most importantly to extend health span, the number of years that we can stay healthy."

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Photo: Muscle regeneration in aging mice. The left photo shows impaired repair of muscle tissue in an aged mouse. The right photo shows improved recovery following cellular reprogramming. Credit: Courtesy of Juan Carlos Izpisua Belmonte Lab /Salk Institute