Did scientists find the key to eternal youth?
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(CNN)
In molecular biologist David Sinclair's lab at Harvard Medical School, old mice are getting young again.
Using proteins that can convert an adult cell into a stem cell, Sinclair and his team have restored aged cells in mice to earlier versions of themselves.
In his team's first breakthrough, published in late 2020, old mice with poor eyesight and damaged retinas were suddenly able to see again, with vision sometimes rivaling that of their young.
"It's a permanent reset, as far as we know, and we think it may be a universal process that could be applied throughout the body to reset our age," said Sinclair, who has spent the last 20 years studying ways to reverse the ravages of time.
"If we reverse aging, these diseases shouldn't happen. Today we have the technology to be able to get to 100 and beyond without worrying about having cancer in your 70s, heart disease in your 80s, and Alzheimer's in your 90s," Sinclair told an audience at Life Itself, a health and wellness event presented in association with CNN.
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"This is the world that is coming. It is literally a question of when and for most of us it will happen in our lifetimes," Sinclair told the audience.
"His research shows that you can change aging so that life is younger for longer. Now he wants to change the world and turn aging into a disease," said Whitney Casey, an investor who partnered with Sinclair to create a home biological age test
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While modern medicine addresses the disease, it doesn't address the underlying cause, "which for most diseases is aging itself," Sinclair said.
"We know that when we reverse the age of an organ like the brain of a mouse, the diseases of aging disappear. The memory returns; there is no more dementia. I think that in the future, delaying and reversing aging will be the best way to treat the diseases that afflict most of us.
a reset button
In Sinclair's lab, two mice sit next to each other.
One is the image of youth, the other gray and weak.
However, they are brother and sister, born from the same litter: only one has been genetically altered to age faster.
If that could be done, Sinclair asked his team, could the reverse be done as well?
The Japanese biomedical researcher, Dr. Shinya Yamanaka, had already reprogrammed adult human skin cells to behave like embryonic or pluripotent stem cells, capable of becoming any cell in the body.
The 2007 discovery earned the scientist a Nobel Prize, and his "induced pluripotent stem cells" soon became known as "Yamanaka factors."
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However, the adult cells fully converted back to stem cells through the Yamanaka factors and lose their identity.
They forget that they are blood cells, heart cells, and skin cells, which makes them perfect for being reborn as "day cells," but lousy for rejuvenation.
You don't want Brad Pitt in "The Curious Case of Benjamin Button" to turn into a baby all at once;
you want him to age backwards while still remembering who he is.
Laboratories around the world jumped on the problem.
A study published in 2016 by researchers at the Salk Institute for Biological Studies in La Jolla, California, showed that signs of aging could be eliminated in genetically aged mice, exposed for a short time to four major Yamanaka factors, without erasing the identity of the cells. cells.
But there was a downside to all this research: In certain situations, the altered mice developed cancerous tumors.
In search of a safer alternative, Sinclair lab geneticist Yuancheng Lu chose three of the four factors and genetically added them to a harmless virus.
The virus was designed to deliver Yamanaka's rejuvenating factors to damaged retinal ganglion cells in the back of an elderly mouse's eye.
After injecting the virus into the eye, the pluripotent genes were activated by feeding the mouse an antibiotic.
"The antibiotic is just a tool. It could be any chemical really, just a way to make sure all three genes are turned on," Sinclair said.
"Normally, they are only on in very young developing embryos and then turn off as we get older."
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Remarkably, the damaged neurons in the eyes of the mice injected with the three cells rejuvenated, even growing new axons or projections from the eye to the brain.
Since that original study, Sinclair said his lab has reversed aging in the muscles and brains of mice and is now working to rejuvenate a mouse's entire body.
"Somehow the cells know that the body can reboot itself and still know which genes should be active when they were young," Sinclair said.
"We think we're tapping into an ancient regeneration system that some animals use: when you cut off a salamander's limb, the limb grows back. A fish's tail will grow back; a mouse's finger will grow back."
That discovery indicates that there is a "backup" of information about youth stored in the body, he added.
"I call it the information theory of aging," he said.
"It's a loss of information that leads aging cells to forget how to function, to forget what kind of cell they are. And now we can harness a reset switch that restores the cell's ability to read the genome correctly again, as if I was young."
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While the changes have lasted for months in mice, the renewed cells don't freeze in time and never age (like, say, vampires or superheroes), Sinclair said.
"It's as permanent as aging. It's a reset, and then we see the mice age again, so we just repeat the process."
"We think we have found the master control switch, a way to rewind the clock," he added.
"Then the body will wake up, it will remember how to behave, it will remember how to regenerate itself, and it will be young again, even if you are already old and have a disease."
Science already knows how to delay human aging
Studies of whether the genetic intervention that reinvigorated mice will do the same for people are in their early stages, Sinclair said.
It will be years before human trials are completed, tested and, if safe and successful, scaled to the mass needed to earn a federal stamp of approval.
While we wait for science to determine whether we, too, can reset our genes, there are plenty of other ways to slow the aging process and reset our biological clocks, Sinclair said.
"The best advice is simply: focus on plants for food, eat less often, get enough sleep, exercise for 10 minutes three times a week to maintain your muscle mass, don't sweat the small stuff, and have a good social group," Sinclair said.
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All of these behaviors affect our epigenome, 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.
What does the epigenome control?
Human behavior and the environment play a key role.
Let's say you were born with a genetic predisposition to heart disease and diabetes.
But because you exercised, ate a plant-based diet, slept well, and managed your stress for most of your life, those genes may never turn on.
This, experts say, is how we can take some of our genetic destiny into our own hands.
The positive impact on our health of eating a plant-based diet, having close and loving relationships, and getting enough exercise and sleep is well documented.
However, calorie restriction is a more controversial way to add years to life, experts say.
Reducing food consumption, without inducing malnutrition, has been a scientifically known way to prolong life for nearly a century.
Studies of worms, crabs, snails, fruit flies and rodents have found that restricting calories "delays the onset of age-related disorders" such as cancer, heart disease and diabetes, according to the National Institute on the Aging.
Some studies have also found extensions in lifespan: In a 1986 study, mice fed just a third of a typical day's calories lived to 53 months;
a mouse kept as a pet can live up to 24 months.
Scientists manage to restore youth to skin cells that have aged
Studies in people, however, have been less enlightening, in part because many have focused on weight loss rather than longevity.
For Sinclair, however, cutting back on meals was a major factor in resetting her personal clock: recent tests show she has a biological age of 42 in a body born 53 years ago.
"I've been doing biotesting for 10 years and I've gotten younger and younger over the last decade," Sinclair said.
"The biggest change in my biological clock happened when I ate less often, now only eating one meal a day. That made the biggest difference in my biochemistry."
Additional ways to turn back the clock
Sinclair incorporates other tools into his life, according to research from his lab and others.
In his book "Lifespan: Why We Age and Why We Don't Have To," he writes that little of what he does has gone through the kind of "rigorous long-term clinical trials" necessary to have a "full understanding of the broad range of possible outcomes.
In fact, he added, "I have no idea if this is the right thing for me."
With that caveat, Sinclair is willing to share his advice: He keeps his starches and sugars to a minimum and ditched desserts at age 40 (although he admits he does indulge on occasion).
He eats a fair amount of plants, avoids eating other mammals, and maintains his body weight at the low end of the optimum.
She works out by taking lots of steps every day, takes the stairs instead of taking an elevator, and visits the gym with her son to lift weights and jog before taking a sauna and taking a dip in an icy pool.
"I got my 20-year-old body back," she said with a smile.
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Speaking of cold, science has long thought that lower temperatures increase longevity in many species, but whether or not that's true may depend on one's genome, according to a 2018 study. Regardless, it seems cold can increase brown fat in humans, which is the type of fat bears use to keep warm during hibernation.
Brown fat has been shown to improve metabolism and fight obesity.
Sinclair takes vitamins D and K2 and baby aspirin every day, along with supplements that have shown promise in extending longevity in yeast, mouse and human cells in test tubes.
One supplement she takes after discovering its benefits is 1 gram of resveratrol, the antioxidant-like substance found in the skin of grapes, blueberries, raspberries, blackberries, and peanuts.
He also takes 1 gram of metformin, a staple in the arsenal of drugs used to lower blood sugar in people with diabetes.
He added it after studies showed it could reduce inflammation, oxidative damage and cellular senescence, in which cells become damaged but refuse to die, remaining in the body as a type of malfunctioning "zombie cell" .
However, some scientists question the use of metformin, pointing to rare cases of lactic acid buildup and a lack of understanding of how it works in the body.
Sinclair also takes 1 gram of NMN, or nicotinamide mononucleotide, which is converted in the body to NAD+, or nicotinamide adenine dinucleotide.
A coenzyme that exists in all living cells, NAD+ plays a central role in biological processes in the body, such as regulating cellular energy, increasing insulin sensitivity, and reversing mitochondrial dysfunction.
As the body ages, NAD+ levels decline significantly, falling in middle age to about half the levels of youth, contributing to age-related metabolic diseases and neurodegenerative disorders.
Numerous studies have shown that restoring NAD+ levels safely improves general health and increases life expectancy in yeast, mice, and dogs.
Clinical trials testing the molecule in humans have been underway for three years, Sinclair said.
"These supplements, and the lifestyle I lead, are designed to activate our defenses against aging," he said.
"Now, if you do that, you won't necessarily turn back the clock. These are just things that slow down epigenetic damage and these other horrible features of aging.
"But the real breakthrough, from my point of view, was the ability to tell the body, 'Forget all that. Go back to being young,' just by flipping a switch. I'm not saying we're all going to be 20 again." Sinclair said.
"But I'm optimistic that we can duplicate this very fundamental process that exists in everything from a bat to a sheep to a whale to a human being. We've done it in a mouse. There's no reason I can think of why not." It should work on one person."
Aging