Cellular Rejuvenation Therapy Safely Reverses Signs of Aging in Mice

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Out in La Jolla, California, a top-ranked research institute has rewound time in mice, resetting their cells to youthful states without stimulating cancer growth, or other disease risk.

The field of studying healthy aging has come up with many ways to promote a longer health span in mice and humans, from grape seed extract, to infusions of gut microbes from younger mice, to using pharmaceuticals which trick your body into fasting.

Well now, it could be as simple as a duplicated molecule known as a “Yamanaka factor” being injected into an area of tissue, and the tissue unwinding years of DNA alteration and damage based on the organism’s interaction with the environment, leaving them with the cells of a young person.

Of course this is only simple because of decades of research in this area. The identification of the Yamanaka factors by Yamanaka Shinya was a huge leap, part of the work for which he won the Nobel Prize for discovering pluripotent stem cells.

At La Jolla, the Salk Institute for Biological Studies found that when mice were injected throughout a period of their life with the four Yamanaka factors, their cells regenerated in a youthful way. How did the scientists determine an older cell from a younger cell? They used epigenetics, which bares an explanation.

Put in a paragraph, epigenetics simply refer to how our genes change over our lives in response to the rigors of life. An “epigenetic change” could be the alteration of glucose metabolism in response to enduring years of famine, such as in the Dutch after World War II. Epigenetics are encoded partly by methyl groups, which if taken off, return cells to more youthful, inexperienced states where all kinds of functions become, at least in the mice, like they were when they were young.

PICTURED: The Nine Hallmarks of Aging, in which DNA damage sustained through life cause the systems of intracellular communication to become obscured, as well as the abilities to repair tissues.

The philosopher’s jab

“At the end of the day, we want to bring resilience and function back to older cells so that they are more resistant to stress, injury and disease,” Pradeep Reddy, a Salk staff scientist and co-first author of the new paper which demonstrated this, told the institute’s press. “This study shows that, at least in mice, there’s a path forward to achieving that”.

In it, study-lead Dr. Juan Carlos Izpisua Belmonte and Reddy tested variations of the cellular rejuvenation approach in healthy animals as they aged. One group of mice received regular doses of the Yamanaka factors from the time they were 15 months old until 22 months, approximately equivalent to age 50 through 70 in humans. Another group was treated from 12 through 22 months, approximately age 35 to 70 in humans, and a third group was treated for just one month at age 25 months, similar to age 80 in humans.

Izpisua Belmonte has shown that Yamanaka factors have rebuilt damaged muscle in mice, but the results of their most recent trial showed that many tissues, including skin, kidney, muscle, and individual cells, all showed signs of the kind of epigenetic patterns one would see in young mice. Moreover, metabolic molecules in the blood of treated animals did not show normal age-related changes, and skin damage from injuries showed fewer signs of scaring and more of whole regeneration.

No blood cell alterations, neurological changes, or signs of cancer were either accelerated or found abnormally, something which, considering the treatment time, could be a concern in humans.

“We are elated that we can use this approach across the lifespan to slow down aging in normal animals. The technique is both safe and effective in mice,” says Izpisua Belmonte. “In addition to tackling age-related diseases, this approach may provide the biomedical community with a new tool to restore tissue and organismal health by improving cell function and resilience in different disease situations, such as neurodegenerative diseases”. WaL

PICTURED ABOVE: A graphic from Salk. PC: Salk Institute. Released.

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