New study reversed aging in mice. Can it work for humans too?
(CNN) — In the Boston labs, old, blind mice have regained their sight, developed smarter, younger brains, and developed healthier muscle and kidney tissue. By contrast, young mice have aged prematurely, with devastating results on nearly every tissue in their bodies.
Experiments show that aging is a reversible process, capable of “going back and forth at will,” says anti-aging 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 store a “backup copy” of our youth that can be activated to regenerate, says Sinclair, lead author of a new paper exposing the work of his lab and international scientists.
The combined experiments, published for the first time Thursday in the academic journal Cell, challenge scientific belief that aging is the result of genetic mutations that undermine our DNA, creating a reservoir of damaged cell tissue that can lead to deterioration, disease and death.
“It’s not the junk, it’s not the damage that makes us old,” says Sinclair, who described the research last year on 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 it forgets how to function, in the same way that software on an old computer can be corrupted. I call it The information theory of aging”.
Jae-Hyun Yang, a genetics researcher at the Sinclair Laboratory and a co-author of the study, says he hopes the findings “will transform the way we view the aging process and approach the treatment of diseases associated with it.”
Epigenetic changes control aging
If we consider DNA as the hardware of the organism, the epigenome would be the software. According to the National Human Genome Research Institute, epigenomes are proteins and chemicals that sit like freckles on each gene, waiting to tell it “what to do, where to do it, and when to do it.”
The epigenome literally turns genes on and off. That process can be triggered by pollution, environmental toxins, and human behaviors like smoking, eating an inflammatory diet, or chronically lacking sleep. And just like a computer, the cellular process becomes corrupted as more DNA is broken or damaged, Sinclair explains.
“The cell panics, and the proteins that would normally control the genes get distracted by having to go repair the 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 don’t find their way back home, much like a person with Alzheimer’s.
“The amazing finding is that there is a backup copy of the software in the body that can be reset,” Sinclair said. “We are demonstrating why that software becomes corrupted and how we can reboot the system using a reset switch that restores the cell’s ability to read the genome again correctly, as if it were young.”
It doesn’t matter if the body is 50 or 75 years old, healthy or afflicted with disease, Sinclair says. Once that process is triggered, “the body will then remember how to regenerate itself and become young again, even if it is already old and has a disease. Now, we don’t know what that software is yet. Right now, we just know that we can trigger 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 aging in yeast. That gene exists in all creatures, so there should be a way to do the same in people, he supposed.
To test the theory, he began trying to speed up aging in mice without causing mutations or cancer.
“We started with that mouse when I was 39 years old. I am now 53 years old and we have been studying that mouse ever since,” she said. “If the information aging theory were wrong, we would get a dead mouse, a normal mouse, an aged mouse, or a mouse with cancer. We get old.”
With the help of other scientists, Sinclair and his Harvard team have managed to age the brain, eye, muscle, skin and kidney tissues of mice.
To do this, Sinclair’s team developed ICE, short for inducible epigenome changes. Instead of altering the coding sections of the mice’s DNA that can trigger mutations, ICE alters the way the DNA folds. The fast-healing temporary cuts made by ICE mimic the daily damage from chemicals, sunlight, and the like that contribute to aging.
At one year old, the ICE mice looked and acted twice their age.
to be young again
Now it was time to reverse the process. Sinclair Lab geneticist Yuancheng Lu created a mixture of three out of four “Yamanaka factors,” adult human skin cells that have been reprogrammed to behave like embryonic or pluripotent stem cells, capable of becoming any cell in the body.
The cocktail was injected into damaged retinal ganglion cells in the back of the eyes of blind mice and activated by feeding them antibiotics.
“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 previously told CNN. “Normally they only turn on in very young developing embryos and then turn off as we get older.”
The mice recovered most of their sight.
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 could cause cancer or worse,” Sinclair said. “Instead, the cells go back to 50 to 75% of their original age, and they stop and don’t get any younger, which is lucky. How cells know to do that, we still don’t understand.”
Currently, Sinclair’s team is trying to find a way to deliver the genetic change evenly to each cell, thereby 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.
“You use the same system that we developed to treat very old mice, the equivalent of an 80-year-old human. And yet they managed to make the mice live longer, which is remarkable. So they have gone ahead of us in that experiment,” he said.
“But that tells me that rejuvenation doesn’t just affect a few organs, it can rejuvenate the whole mouse because they live longer,” he added. “The results are a gift and a confirmation of what our article says.”
Whats Next? Billions of dollars are being poured into anti-aging, funding all sorts of methods to turn back the clock.
Sinclair says that in his lab his team has reset cells in mice multiple times, showing that aging can be reversed more than once, and is currently testing genetic reset in primates. But it could be decades before any human anti-aging clinical trial begins, is analyzed and, if safe and successful, scaled up for federal approval.
But just as damaging factors can alter the epigenome, healthy behaviors can repair it, Sinclair said.
“We know that this is probably true because people who have led a healthy lifestyle are of younger biological age than those who have done the opposite,” he said.
His best tips? Focus on eating plants, eating less often, getting enough sleep, getting out of breath for 10 minutes three times a week exercising to maintain muscle mass, not worrying about the small stuff, and having a good social group.
“The message is that every day counts,” Sinclair said. “How you live your life, even in your teens or early 20s, really matters, even decades later, because your clock is ticking every day.”