Using proteins that can turn an adult cell into a stem cell, David Sinclair and his team reverted aging mouse cells to their earlier versions. In his team’s first breakthrough, published in late 2020, old mice with poor vision and damaged retinas were suddenly able to see again, with vision that at times rivaled that of their offspring, CNN tells CNN.
“As far as we can tell, this is a permanent reset, and we think it could be a universal process that can be applied to the entire body to reset our age,” said Sinclair, who has been studying ways to reverse the ravages of time for the past 20 years.
“If we reverse aging, these diseases should not exist. Today, we have the technology to live to 100 without worrying about cancer at 70, heart disease at 80, and Alzheimer’s at 90,” David Sinclair said at a health and wellness event presented in partnership with CNN.
“This is the world to come. It’s literally a matter of when and for most of us this will happen in our lives,” Sinclair told his listeners.
“His research shows that you can reverse aging to make life younger for longer. Now he wants to change the world and make aging a disease,” says investor Whitney Casey, who is collaborating with Sinclair.
While modern medicine treats disease, it doesn’t address the root cause, “which for most diseases is aging itself,” says Sinclair. “We know that when we reverse the age of an organ like the brain of a mouse, the diseases of aging disappear. Memory returns, dementia is gone. I believe that in the future, slowing down and reversing aging will be the best way to treat the diseases that plague most of us.”
Two mice sit side by side in Sinclair’s lab. One is a picture of youth, the other is gray-haired and weak. However, they are siblings born from the same litter – only one of them has been genetically altered to age faster.
If it’s possible, Sinclair asked his team if it’s possible to do the opposite? Japanese biomedical researcher Dr. Shinya Yamanaka has already reprogrammed adult skin cells to behave like embryonic or pluripotent stem cells, capable of developing into any cell in the body. The discovery in 2007 brought the scientist a Nobel Prize, and his “induced pluripotent stem cells” soon became known as the “Yamanaka factors.”
However, adult cells fully switched back to stem cells by Yamanaka factors lose their identity. They forget that they are blood, heart, and skin cells, making them ideal for resurrection as “day cells” but poor for rejuvenation. You don’t want, notes CNN, that Brad Pitt from The Curious Case of Benjamin Button suddenly becomes a child; you want him to grow old but still remember who he is.
Laboratories around the world have seized on this problem. A study published in 2016 by scientists at the Salk Institute for Biological Research in La Jolla, California showed that signs of aging can disappear in genetically aged mice exposed to short-term exposure to the four main Yamanaka factors, without erasing cell identity.
But all of these studies had a downside: in certain situations, the modified mice developed cancerous tumors.
In search of a safer alternative, Yuancheng Lu, a geneticist at Sinclair’s lab, selected 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 at the back of the old mouse’s eye. After injecting the virus into the eye, the pluripotent genes were turned on by feeding mice an antibiotic.
“The antibiotic is just a tool. It could actually be any chemical, just a way to make sure three genes are turned on,” says Sinclair. “They are usually turned on only in very young developing embryos and then turned off as they age.”
Surprisingly, damaged neurons in the eyes of mice injected with three cells were rejuvenated. Sinclair said that since this initial study, his lab has reversed muscle and brain aging in mice and is now working to rejuvenate the entire body of the mouse.
“Somehow the cells know that the body can reset itself, and they still know which genes should be turned on 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 limb from a salamander, it grows back. The tail of the fish grows back, the finger of the mouse grows back.”
This discovery indicates that the body stores a “backup copy” of information about youth, the scientist added.
“I call it the information theory of aging,” he said. “It’s a loss of information that causes senescent cells to forget how to function, forget which cell type they are.”
While in mice the changes take months, the new cells don’t freeze over time and never age, Sinclair says. “It’s as permanent as aging. It’s a reboot and then we see the mice age again, so we just repeat the process. We think we’ve found a master control switch, a way to turn the clock back,” he added. “Then the body will wake up, remember how to behave, remember how to regenerate, and be young again, even if you are already old and sick.”
Research into whether the genetic intervention that brought the mice back to life will affect humans is in its early stages, Sinclair said. It will be years before human trials are completed, analyzed and, if safe and successful, scaled up to the mass needed to gain government approval.
As we wait for science to determine whether we can reset our genes, there are plenty of other ways to slow down the aging process and reset our biological clock, Sinclair says.
“The top tips are simple: focus on plant-based food, eat less often, get enough sleep, hold your breath for 10 minutes three times a week while doing muscle-building exercises, take it easy, and have fun in a good social group,” says Sinclair.
All of these behaviors affect our epigenome, the proteins and chemicals that sit like freckles on every gene, waiting to tell the gene “what to do, where to do it, and when to do it. What controls the epigenome? Human behavior and its environment play a key role. Let’s say you were born with a genetic predisposition to heart disease and diabetes. But because you’ve been exercising, eating a plant-based diet, sleeping well, and coping with stress for most of your life, it’s possible that these genes never get activated. Experts say this is how we can take some of our genetic destiny into our own hands.
The positive impact on our health of a plant-based diet, close, loving relationships, sufficient exercise and sleep is well documented. Experts say calorie restriction, however, is a more controversial way to increase lifespan.
According to the National Institute on Aging, studies on worms, crabs, snails, fruit flies and rodents have shown that calorie restriction “delays the onset of age-related diseases” such as cancer, heart disease and diabetes. Some studies have also found an increase in lifespan: in a 1986 study, mice given only a third of their usual daily calories lived to 53 months – a mouse kept as a pet could live for about 24 months.
However, human studies have been less informative, in part because many have focused on weight loss rather than longevity. For Sinclair, however, cutting back on meals has been a major factor in resetting his personal clock: recent tests have shown his biological age to be 42, when his real age is 53.
“I’ve been doing biological testing for 10 years now, and I’ve been steadily getting younger over the last decade,” Sinclair said. “The biggest change in my biological clock happened when I ate less frequently — now I only eat once a day. It had the biggest impact on my biochemistry.”
Sinclair uses other tools in his life, based on the research of his laboratory and others. In his book Lifespan: Why We Age and Why We Don’t Need It, he writes that little of what he does has been subjected to the kind of “rigorous long-term clinical trials” needed to “completely understand the wide range of possible outcomes.” . In fact, he added, “I have no idea if I should be doing this.”
With this caveat, Sinclair is ready to share his advice: he keeps starch and sugar intake to a minimum and gave up desserts at 40. He eats a large amount of plant foods, avoids eating mammalian meat, and keeps his body weight at a low, optimal level. He works out by taking many steps every day, walks stairs instead of taking elevators, and visits the gym with his son to lift weights and jog before going to the sauna and taking a dip in an ice-cold water pool. “I got my 20-year-old body back,” he says with a smile.
Speaking of cold, science has long believed that cooler temperatures increase lifespan in many species, but according to a 2018 study, whether this is true or not may depend on the human genome.