Old mice get younger during the study. Can people do the same?

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

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

Experiments show that aging is a reversible process, capable of being driven “back and forth at will,” said anti-aging expert David Sinclair, a professor of genetics at Harvard Medical School’s Blavatnik Institute. and co-director of the Paul F. Glenn Center. for research in the biology of aging.

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

The combined experiments, first published Thursday in the journal Cell, challenge the scientific belief that aging is the result of genetic mutations that undermine our DNA, creating a dumping ground for damaged cell tissue that can lead to deterioration, disease and death.

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

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

Jae-Hyun Yang, a genetics researcher at Sinclair Lab and co-author of the paper, said he expects the results to “transform the way we view the aging process and our approach to treating disease. associated with aging.

Epigenetic changes control aging

While DNA can be thought of 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, following an inflammatory diet, or suffering from chronic lack of sleep. And just like a computer, the cellular process is corrupted as more DNA is broken or damaged, Sinclair said.

“The panic cell and the proteins that normally control genes are distracted by the need to go and repair DNA,” he explained. “Then they don’t all find their way back to where they started, so over time it’s like a game of ping pong, where the balls end up all over the floor.”

In other words, the cellular pieces lose their way home, much like someone with Alzheimer’s disease.

“The amazing discovery is that there is a backup copy of the software in the body that you can reset,” Sinclair said. “We show why this software is corrupted and how we can reboot the system by pressing a reset switch that restores the cell’s ability to correctly read the genome, as if it were young.”

It doesn’t matter if the body is 50 or 75, healthy or in the throes of disease, Sinclair said. Once this process is triggered, “the body will then remember how to regenerate and become young again, even if you are already old and have a disease. Now what this software is, we don’t know yet. At this stage point, we just know we can flip the switch.”

Every day counts. How you live your life, even when you’re a teenager and in your twenties, really matters, even decades later, because every day your clock is ticking.

– Anti-aging expert David Sinclair

years of research

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

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

“We started making this mouse when I was 39. I’m now 53 and we’ve been studying this mouse ever since,” he said. “If the information aging theory were wrong, then we’d either have a dead mouse, a normal mouse, an aging mouse, or a mouse with cancer. We’re getting old.”

With the help of other scientists, Sinclair and his team at Harvard were able to age the brain, eye, muscle, skin and kidney tissue of mice.

To do this, Sinclair’s team developed ICE, short for inducible changes in the epigenome. Instead of altering the coding sections of mouse DNA that can trigger mutations, ICE alters the way DNA is folded. Fast-healing temporary cuts made by ICE mimic daily damage from chemicals, sunlight and more that contribute to aging.

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

Become young again

Now was the time to reverse the process. Sinclair Lab geneticist Yuancheng Lu has created a mixture of three of the four “Yamanaka Factors”, human adult skin cells that have been reprogrammed to behave like embryonic or pluripotent stem cells, capable of developing into any which cell of the body.

The cocktail was injected into damaged retinal ganglion cells at the back of the eyes of blind mice and activated by feeding mice antibiotics.

“The antibiotic is just a tool. It can be any chemical, just a way to make sure all three genes are turned on,” Sinclair told CNN. “Normally they are only activated in very young developing embryos and then switch off as we get older.”

The mice regained most of their sight.

Next, the team tackled 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, mice don’t go back to age zero, which would cause cancer or worse,” Sinclair said. “Instead, the cells come back to between 50% and 75% of their original age, and they shut down and don’t get any younger, which is lucky. How do cells know how to do that, we don’t know. don’t understand yet.”

“Every day counts”

Now Sinclair’s team is trying to find a way to deliver the genetic switch evenly to every 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. And they still made the mice live longer, which is remarkable. They gave us therefore in a way ahead of it.” in this experience,” he said.

“But that tells me that rejuvenation doesn’t just affect a few organs, it’s able to rejuvenate the whole mouse because they live longer,” he added. “The results are a gift and a confirmation of what our newspaper says.”

And after? Billions of dollars are invested in the fight against aging, funding all sorts of methods to turn back the clock.

In his lab, Sinclair said his team has reset cells in mice multiple times, showing that aging can be reversed more than once, and he is currently testing genetic reset in primates. But decades could pass before any anti-aging human clinical trials begin, be analyzed and, if safe and successful, scaled up 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 that’s probably true because people who lived healthy lives are younger in biological age than those who did the opposite,” he said.

His good plans? Focus on plants for nourishment, eat less often, get enough sleep, lose your breath for 10 minutes three times a week exercising to maintain muscle mass, don’t sweat the small stuff, and have a good band social.

“The message is that every day counts,” Sinclair said. “How you live your life, even when you’re a teenager and in your twenties, really matters, even decades later, because every day your clock is ticking.”

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