Scientists managed to restore youth to old mice: rejuvenation of people is next

In Boston labs, old blind mice regained their sight, developed smarter and younger brains, and developed healthier muscle and kidney tissue. What is happening and is it possible to reverse human aging in this way, the publication said CNN.

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Experiments show that aging is a reversible process that can move "back and forth at will," says anti-aging expert David Sinclair, professor of genetics at Harvard Medical School's Blavatnik Institute and co-director of the Paul Glenn Center for the Biology of Aging Research.

“Our bodies store a backup copy of our youth that can be triggered to regenerate,” Sinclair assured.

The combined experiments, first published in the journal Cell, challenge the scientific belief that aging is the result of genetic mutations. These mutations undermine our DNA and create a dump of damaged cellular tissue that can lead to deterioration, disease, and death.

“We don't age because of damage,” said Sinclair, who described the work last year at Life Itself, a health and wellness event. “We think it's information loss—the loss of the cell's ability to read its original DNA, causing it to forget how to function.” I call it the information theory of aging."

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Jae-Hyun Yang, a researcher in the Sinclair lab who is a co-author of the paper, expects the results to "change the way we think about aging and how we treat aging-related diseases."

Epigenetic changes control aging

DNA can be thought of as the hardware of the body, while the epigenome is the software. According to the National Human Genome Research Institute, epigenes are proteins and chemicals that sit like freckles on each gene, waiting to tell the gene “what to do, where to do it, and when to do it.”

The epigenome literally turns genes on and off. This process can be caused by environmental pollution, environmental toxins, and human behavior such as smoking, eating unhealthy foods, or chronic sleep deprivation. And just like a computer, the cellular process becomes damaged as more DNA is broken or damaged, Sinclair said.

“The cell panics, and the proteins that normally control the genes are diverted to go and repair the DNA,” he explained. “Then they don’t all end up back where they started, so over time it’s like a ping-pong match where the balls end up all over the floor.”

That is, pieces of the cell lose their way home, like a person with Alzheimer's disease.

“The surprising discovery is that there is a software backup in the body that you can activate,” Sinclair explained.

According to him, it doesn't matter if you are 50 or 75 years old, healthy or sick. Once this process is started, “the body will remember how to regenerate and become young again, even if you are already old and sick. What kind of program it is, we don't know yet. For now, one thing is known: we can flip the switch.”

Years of research

The hunt for the switch began when Sinclair was a graduate student on the MIT team that discovered the existence of genes that control aging in yeast. This gene exists in all creatures, so there must be a way to do the same in humans, he suggested.

To test the theory, the graduate student began trying to speed up aging in mice without causing mutations or cancer.

“We started studying this mouse when I was 39 years old. I’m 53 years old now, and we’ve been studying this mouse ever since,” he said. “If the information aging theory were wrong, we would end up with a dead mouse, a regular mouse, an aging mouse, or a mouse with cancer.”

With the help of other scientists, Sinclair and his Harvard team were able to age tissue from the brain, eyes, muscles, skin, and kidneys of mice.

To do this, Sinclair's team developed ICE, short for induced changes in the epigenome. Instead of changing the coding regions of mouse DNA that can cause mutations, ICE changes the way DNA folds. The temporary, fast-healing incisions made by ICE mimic the daily damage from chemicals, sunlight, and the like that contribute to aging.

Become young again

Now it's time to reverse the process. Sinclair Lab geneticist Yuancheng Lu created a mixture of three of the four "Yamanaka factors," adult human skin cells that have been reprogrammed to behave like embryonic or pluripotent stem cells, capable of developing into any cell in the body.

The cocktail was injected into damaged retinal ganglion cells at the back of the eyes of blind mice and turned them on with antibiotics.

“An antibiotic is just a tool. In fact, it could be any chemical,” Sinclair said.

The mice regained most of their vision. Then, according to the study, the team took brain, muscle, and kidney cells and restored them to much younger levels.

“One of the things we learned was that if you use this particular set of three pluripotent stem cells, the mice don't go back to age zero, which can cause cancer or worse,” Sinclair explained. “Instead, the cells return to 50-75% of their original age, stop and don’t get any younger, which is very good. We don’t yet understand how cells know this.”

Today, Sinclair's team is trying to find a way to evenly deliver the genetic switch to each cell, thus rejuvenating the entire mouse at once.

“Delivery is a technical hurdle, but other groups of researchers seem to have succeeded on this,” Sinclair said, pointing to two unpublished studies that appear to have solved the problem.

“One uses the same system we developed to treat very old mice, equivalent to an 80-year-old person. And they still made the mice live longer, which is remarkable. So they were kind of ahead of us in this experiment,” he said. “But this tells me that rejuvenation doesn’t just affect a few organs, it can rejuvenate the entire mouse.”

What's next? Billions of dollars are pouring into the fight against aging by funding all sorts of methods to turn back the clock.

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Sinclair said his team has aged cells several times in mice showing that aging can be reversed more than once, and he is currently testing the genetic reset in primates. But it could be decades before any human anti-aging clinical trials get underway, analyzed and, if safe and successful, scaled up to the masses needed for federal approval.

But just as damaging factors can destroy the epigenome, healthy behavior can restore it, Sinclair argued.

“We know that this is probably true, because people who led a healthy lifestyle have a lower biological age than those who did the opposite,” he stressed.

His top tips? Focus on plants for food, eat less often, get enough sleep, exercise to maintain muscle mass.

“Every day counts,” Sinclair remarked. “How you live your life, whether it’s in your teens or 20s, really matters even decades later because every day your clock is ticking.”

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