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Old mice become young again in the study. Can people do the same?

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These mice are from the same litter. The one on the right has been genetically altered to age. (David Sinclair)

Estimated reading time: 7-8 minutes

BOSTON — In a laboratory experiment, old, blind mice regained their sight, developed younger, smarter brains, and built healthier muscle and kidney tissue. Young mice, on the other hand, aged prematurely, with devastating results for almost every tissue in their bodies.

The experiments show that aging is a reversible process, capable of being driven “back and forth at will,” said antiaging expert David Sinclair, professor of genetics at the Blavatnik Institute at Harvard Medical School and co-director of the Paul F. Glenn Center. for Research in the Biology of Aging.

Our bodies have a backup copy of our youth that can be triggered to regenerate, said Sinclair, senior author of a new paper that features work from his lab and international scientists.

The combined experiments, first published in the journal Cell, challenge the scientific belief that aging is the result of genetic mutations that damage our DNA, creating a junkyard of damaged cellular tissue that can lead to decay, disease and death.

“It’s not junk, it’s not damage that makes us age,” said Sinclair, who described the work last year on Life Itself, a health and wellness event presented in partnership with CNN.

“We believe it’s a loss of information – a loss of the cell’s ability to read its original DNA so it forgets how to function – in the same way an old computer can develop corrupt software. I call this the information theory of aging .”

Jae-Hyun Yang, a Sinclair Lab genetics researcher and co-author of the paper, said he hoped the findings “transform the way we view the aging process and the way we approach treating diseases associated with aging.”

Epigenetic changes control aging

While DNA can be seen as the hardware of the body, the epigenome is the software. 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,” according to the National Human Genome Research Institute.

The epigenome literally turns genes on and off. This process can be triggered by pollution, environmental toxins, and human behaviors such as smoking, eating an inflammatory diet, or suffering from a chronic lack of sleep. And just like a computer, the cellular process becomes corrupted as more DNA is broken or damaged, Sinclair said.

“The cell panics and the proteins that would normally control the genes are distracted by having to repair the DNA,” he explained. “So not everyone finds their way back to where they started, so over time it’s like a ping-pong match, where the balls end up all over the floor.”

In other words, cellular parts lose their way back home, like a person with Alzheimer’s.

“The surprising finding is that there’s a backup copy of the software in the body that you can reset,” Sinclair said. “We’re showing why this software got corrupted and how we can reset the system by tapping a reset button that restores the cell’s ability to read the genome correctly again, as if it were young.”

It doesn’t matter if the body is 50 or 75, healthy or ravaged by disease, Sinclair said. Once this process has been triggered, “the body will remember how to regenerate itself and will be young again, even if you are already old and have an illness. Now, what this software is, we still don’t know. At this point, we we just know we can flip the switch.”

Every day counts. How you live your life, even in your teens and 20s, really matters even decades later because every day your clock is ticking.

– Anti-aging expert David Sinclair

years of research

The quest for change began when Sinclair was a graduate student, part of a team at the Massachusetts Institute of Technology that discovered the existence of genes to control yeast aging. That gene exists in all creatures, so there must be a way to do the same in people, he guessed.

To test the theory, he began trying to accelerate aging in mice without causing mutations or cancer.

“We started making that mouse when I was 39. Now I’m 53, and we’ve been studying that mouse ever since,” he said. “If the information aging theory were wrong, we would have a dead mouse, a normal mouse, an aged mouse or a mouse with cancer. We age.”

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

To do this, Sinclair’s team developed ICE, short for inducible changes in the epigenome. Instead of changing the coding sections of the mice’s DNA that can trigger mutations, ICE changes the way the DNA is folded. The fast-healing temporary cuts made by ICE mimic the daily damage caused by chemicals, sunlight, and the like that contribute to aging.

One-year-old ICE mice looked and acted twice their age.

Becoming young again

Now it was time to reverse the process. Sinclair Lab geneticist Yuancheng Lu has created a blend 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 transforming 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 activated by feeding them antibiotics.

“The antibiotic is just a tool. It could really be any chemical, just a way to make sure the three genes are turned on,” Sinclair told CNN earlier. “Typically, they’re only in very young developing embryos, and then they switch off as we get older.”

The mice regained most of their vision.

Next, the team targeted brain, muscle and kidney cells and restored them to much younger levels, according to the study.

“One of our breakthroughs was realizing that if you use this particular set of three pluripotent stem cells, the mice don’t go back to age zero, which would cause cancer or worse,” Sinclair said. “Instead, the cells go back to between 50% and 75% of their original age, stop and don’t get any younger, which is fortunate. How the cells know to do this, we still don’t understand.”

‘Every day counts’

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

“Delivery is a technical hurdle, but other groups seem to have done well,” Sinclair said, pointing to two unpublished studies that appear to have overcome the problem.

“One uses the same system that we developed to treat very old mice, the equivalent of an 80-year-old human being. And they even got the mice to live longer, which is remarkable. So they kind of beat us to the punch in this experiment.” , he said.

“But this tells me that the rejuvenation is not just affecting a few organs, it is able to rejuvenate the whole mouse because they are living longer,” he added. “The results are a gift and a confirmation of what our newspaper is saying.”

What is the next? Billions of dollars are being invested in anti-aging, funding all sorts of methods to turn back the clock.

In his lab, Sinclair said his team reset cells in mice multiple times, showing that aging can be reversed more than once, and he is currently testing genetic resetting in primates. But decades could pass before any human anti-aging clinical trials begin, are analyzed and, if safe and successful, scaled to the mass needed for federal approval.

But just as damaging factors can disrupt the epigenome, healthy behaviors can repair it, Sinclair said.

“We know this is probably true because people who lead a healthy lifestyle have a lower biological age than those who do the opposite,” he said.

Your top tips? Focus on plants as food, eat less often, get enough sleep, get out of breath for 10 minutes three times a week, exercise to maintain your muscle mass, don’t worry about the little things, and have a good social group.

“The message is that every day counts,” Sinclair said. “How you live your life, even in your teens and 20s, really matters even decades later because every day your clock is ticking.”

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