Old mice become young again in the study. Can humans do the same? (2023)

In Boston labs, old and blind miceYou got your sight back, they developed younger, smarter brains and built healthier muscle and kidney tissue. Young mice, on the other hand, aged prematurely, with devastating consequences for almost every tissue in their bodies.

Experiments show that aging areversible process that "can be pushed back and forth at will," said anti-aging expert David Sinclair, professor of genetics at Harvard Medical School's Blavatnik Institute and co-directorVom Paul F. Glenn Center for the Biology of Aging Research.

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

The combined experimentsFirst published Thursday in Cell Magazine, challenge the scientific belief that aging is the result of genetic mutations that erode our DNA and create a junkyard of damaged cellular tissue that can lead to deterioration, disease and death.

"It's not junk, it's not damage that ages us," said Sinclair, whodescribed working on Life Its last year,a health and wellness event presented in association 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 it works, in the same way an old computer can develop corrupted software. I call this information theory. of aging”.

Jae-Hyun Yang, genetics researcher fromsinclair labwho is a co-author of the paper, said he hoped the findings "change the way we view the aging process and how we approach treating diseases associated with aging."

Epigenetic changes control aging

While DNA can be thought of as the body's hardware, 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, an inflammatory diet, or chronic lack of sleep. And just like a computer, the more DNA is broken or damaged, the cellular process becomes corrupted, Sinclair said.

"The cell panics and the proteins that normally control genes are distracted from DNA repair," he explained. "So not everyone finds their way back to where they started, over time it's like a ping-pong game where the balls fall all over the floor."

In other words, parts of the cells lose their way back home, as in a person with Alzheimer's.

"The surprising result is that there is a backup copy of the software in the body that can be restored," said Sinclair. "We show why this software gets corrupted and how we can reset the system by flipping a reset button that restores the cell's ability to read the genome correctly the way it was young."

It doesn't matter if the body is 50 or 75, healthy or sick, Sinclair said. Once this process is triggered, "even if you are already old and have an illness, the body will remember how to regenerate itself and become young again. Well, what that software is, we still don't know. At this point." , all we know is that we can flip the switch."

years of research

The search for the switch 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. This gene exists in all creatures, so there must be a way to do the same in humans, he said.saying

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

"We started making this mouse when I was 39. I'm 53 now and we've been studying this mouse ever since," he said. "If the information theory of aging were wrong, we would have a dead mouse, a normal mouse, an old mouse or a mouse with cancer. We have aging."

With the help of other scientists, Sinclair and his Harvard team managed to age the brain, eyes, muscles, skin and kidney tissues of mice.

To do this, Sinclair's team developed ICE, short for inducible changes in the epigenome. Rather than altering the coding sections of the mouse's DNA that can trigger mutations, ICE changes the way the DNA folds. ICE's fast-healing temporary incisions mimic the daily damage caused by chemicals, sunlight, and the like that contribute to aging.

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

be young again

Now it was time to reverse the process. Sinclair Lab geneticist Yuancheng Lu developed a three-in-four blend."Fatores Yamanaka, “cells from adult human skin 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 in the fundus of blind mice and activated by feeding.antibiotics for mice

“The antibiotic is just a tool. It could actually be any chemical, just a way to make sure all three genes are turned on," Sinclair told CNN. "Usually they only turn on in very young developing embryos and then turn 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, by using this particular set of three pluripotent stem cells, the mice didn't go back to age zero, which could cause cancer or worse," Sinclair said. “Instead, the cells go back to 50 to 75% of their original age and stop and don't get any younger, which is lucky. We still don't understand how the cells know this."

Today, Sinclair's team is trying to find a way to apply the genetic modification to each cell equally, 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.

“They use the same system that we developed to treat very old mice, equivalent to an 80-year-old human being. And they even managed to make the mice live longer, which is remarkable. So they beat us to that experiment.", she said.

"But what this tells me is that rejuvenation doesn't just affect a few organs, it can rejuvenate the entire mouse because it lives longer," he added. "The results are a gift and a confirmation of what our article says."

What is the next? Billions of dollars are being invested in anti-aging and 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 is currently testing genetic resetting in primates. But it could be decades before any anti-aging clinicHuman trials begin, are tested, and if safe and successful are scaled up to the required mass for federal approval.

But just as damaging factors can alter the epigenome, healthy behavior can repair it, Sinclair said.

"We know this is probably true because people who have healthy lifestyles have younger biological ages than those who don't," he said.

Your top tips? Focus on plants as food, eat less often,Get plenty of sleep, be out of breath for 10 minutes three times a week, exercise to maintain muscle mass, don't worry about trifles, and have a good social group.

"The message is that every day counts," Sinclair said. "How do you live your life, even as a teenager andYour 20s are very important, even decades later, because your clock is ticking every day."