Aubrey de Grey at the World Stem Cell Summit in Miami on January 25, 2018.
Aging is not a mystery, says famed researcher Dr. Aubrey de Grey, perhaps the world's foremost advocate of the provocative view that medical technology will one day allow humans to control the aging process and live healthily into our hundreds—or even thousands.
"The cultural attitudes toward all of this are going to be completely turned upside down by sufficiently promising results in the lab, in mice."
He likens aging to a car wearing down over time; as the body operates normally, it accumulates damage which can be tolerated for a while, but eventually sends us into steep decline. The most promising way to escape this biological reality, he says, is to repair the damage as needed with precise scientific tools.
The bad news is that doing this groundbreaking research takes a long time and a lot of money, which has not always been readily available, in part due to a cultural phenomenon he terms "the pro-aging trance." Cultural attitudes have long been fatalistic about the inevitability of aging; many people balk at the seemingly implausible prospect of indefinite longevity.
But the good news for de Grey—and those who are cheering him on—is that his view is becoming less radical these days. Both the academic and private sectors are racing to tackle aging; his own SENS Research Foundation, for one, has spun out into five different companies. Defeating aging, he says, "is not just a future industry; it's an industry now that will be both profitable and extremely good for your health."
De Grey sat down with Editor-in-Chief Kira Peikoff at the World Stem Cell Summit in Miami to give LeapsMag the latest scoop on his work. Here is an edited and condensed version of our conversation.
Since your book Ending Aging was published a decade ago, scientific breakthroughs in stem cell research, genome editing, and other fields have taken the world by storm. Which of these have most affected your research?
They have all affected it a lot in one way, and hardly at all in another way. They have speeded it up--facilitated short cuts, ways to get where we're already trying to go. What they have not done is identified any fundamental changes to the overall strategy. In the book, we described the seven major types of damage, and particular ways of going about fixing each of them, and that hasn't changed.
"Repair at the microscopic level, one would be able to expect to do without surgery, just by injecting the right kind of stem cells."
Has any breakthrough specifically made the biggest impact?
It's not just the obvious things, like iPS (induced pluripotent stem cells) and CRISPR (a precise tool for editing genes). It's also the more esoteric things that applied specifically to certain of our areas, but most people don't really know about them. For example, the identification of how to control something called co-translational mitochondrial protein import.
How much of the future of anti-aging treatments will involve regeneration of old tissue, or wholesale growth of new organs?
The more large-scale ones, regenerating whole new organs, are probably only going to play a role in the short-term and will be phased out relatively rapidly, simply because, in order to be useful, one has to employ surgery, which is really invasive. We'll want to try to get around that, but it seems quite likely that in the very early stages, the techniques we have for repairing things at the molecular and cellular level in situ will be insufficiently comprehensive, and so we will need to do the more sledgehammer approach of building a whole new organ and sticking it in.
Every time you are in a position where you're replacing an organ, you have the option, in principle, of repairing the organ, without replacing it. And repair at the microscopic level, one would be able to expect to do without surgery, just by injecting the right kind of stem cells or whatever. That would be something one would expect to be able to apply to someone much closer to death's door and much more safely in general, and probably much more cheaply. One would expect that subsequent generations of these therapies would move in that direction.
Your foundation is working on an initiative requiring $50 million in funding—
Well, if we had $50 million per year in funding, we could go about three times faster than we are on $5 million per year.
And you're looking at a 2021 timeframe to start human trials?
That's approximate. Remember, because we accumulate in the body so many different types of damage, that means we have many different types of therapy to repair that damage. And of course, each of those types has to be developed independently. It's very much a divide and conquer therapy. The therapies interact with each other to some extent; the repair of one type of damage may slow down the creation of another type of damage, but still that's how it's going to be.
And some of these therapies are much easier to implement than others. The easier components of what we need to do are already in clinical trials—stem cell therapies especially, and immunotherapy against amyloid in the brain, for example. Even in phase III clinical trials in some cases. So when I talk about a timeframe like 2021, or early 20s shall we say, I'm really talking about the most difficult components.
What recent strides are you most excited about?
Looking back over the past couple of years, I'm particularly proud of the successes we've had in the very most difficult areas. If you go through the 7 components of SENS, there are two that have absolutely been stuck in a rut and have gotten nowhere for 15 to 20 years, and we basically fixed that in both cases. We published two years ago in Science magazine that essentially showed a way forward against the stiffening of the extracellular matrix, which is responsible for things like wrinkles and hypertension. And then a year ago, we published a real breakthrough paper with regard to placing copies of the mitochondria DNA in the nuclear DNA modified in such a way that they still work, which is an idea that had been around for 30 years; everyone had given up on it, some a long time ago, and we basically revived it.
A slide presented by Aubrey de Grey, referencing his collaboration with Mike West at AgeX, showing the 7 types of damage that he believes must be repaired to end aging.
(Courtesy Kira Peikoff)
That's exciting. What do you think are the biggest barriers to defeating aging today: the technological challenges, the regulatory framework, the cost, or the cultural attitude of the "pro-aging" trance?
One can't really address those independently of each other. The technological side is one thing; it's hard, but we know where we're going, we've got a plan. The other ones are very intertwined with each other. A lot of people are inclined to say, the regulatory hurdle will be completely insurmountable, plus people don't recognize aging as a disease, so it's going to be a complete nonstarter. I think that's nonsense. And the reason is because the cultural attitudes toward all of this are going to be completely turned upside down before we have to worry about the regulatory hurdles. In other words, they're going to be turned upside down by sufficiently promising results in the lab, in mice. Once we get to be able to rejuvenate actually old mice really well so they live substantially longer than they otherwise would have done, in a healthy state, everyone's going to know about it and everyone's going to demand – it's not going to be possible to get re-elected unless you have a manifesto commitment to turn the FDA completely upside down and make sure this happens without any kind of regulatory obstacle.
I've been struggling away all these years trying to bring little bits of money in the door, and the reason I have is because of the skepticism as to regards whether this could actually work, combined with the pro-aging trance, which is a product of the skepticism – people not wanting to get their hopes up, so finding excuses about aging being a blessing in disguise, so they don't have to think about it. All of that will literally disintegrate pretty much overnight when we have the right kind of sufficiently impressive progress in the lab. Therefore, the availability of money will also [open up]. It's already cracking: we're already seeing the beginnings of the actual rejuvenation biotechnology industry that I've been talking about with a twinkle in my eye for some years.
"For humans, a 50-50 chance would be twenty years at this point, and there's a 10 percent chance that we won't get there for a hundred years."
Why do you think the culture is starting to shift?
There's no one thing yet. There will be that tipping point I mentioned, perhaps five years from now when we get a real breakthrough, decisive results in mice that make it simply impossible to carry on being fatalistic about all this. Prior to that, what we're already seeing is the impact of sheer old-school repeat advertising—me going out there, banging away and saying the same fucking thing again and again, and nobody saying anything that persuasively knocks me down. … And it's also the fact that we are making incremental amounts of progress, not just ourselves, but the scientific community generally. It has become incrementally more plausible that what I say might be true.
I'm sure you hate getting the timeline question, but if we're five years away from this breakthrough in mice, it's hard to resist asking—how far is that in terms of a human cure?
When I give any kind of timeframes, the only real care I have to take is to emphasize the variance. In this case I think we have got a 50-50 chance of getting to that tipping point in mice within five years from now, certainly it could be 10 or 15 years if we get unlucky. Similarly, for humans, a 50-50 chance would be twenty years at this point, and there's a 10 percent chance that we won't get there for a hundred years.
"I don't get people coming to me saying, well I don't think medicine for the elderly should be done because if it worked it would be a bad thing. People like to ignore this contradiction."
What would you tell skeptical people are the biggest benefits of a very long-lived population?
Any question about the longevity of people is the wrong question. Because the longevity that people fixate about so much will only ever occur as a side effect of health. However long ago you were born or however recently, if you're sick, you're likely to die fairly soon unless we can stop you being sick. Whereas if you're healthy, you're not. So if we do as well as we think we can do in terms of keeping people healthy and youthful however long ago they were born, then the side effect in terms of longevity and life expectancy is likely to be very large. But it's still a side effect, so the way that people actually ought to be—in fact have a requirement to be—thinking, is about whether they want people to be healthy.
Now I don't get people coming to me saying, well I don't think medicine for the elderly should be done because if it worked it would be a bad thing. People like to ignore this contradiction, they like to sweep it under the carpet and say, oh yeah, aging is totally a good thing.
People will never actually admit to the fact that what they are fundamentally saying is medicine for the elderly, if it actually works, would be bad, but still that is what they are saying.
Shifting gears a bit, I'm curious to find out which other radical visionaries in science and tech today you most admire?
Fair question. One is Mike West. I have the great privilege that I now work for him part-time with Age X. I have looked up to him very much for the past ten years, because what he did over the past 20 years starting with Geron is unimaginable today. He was working in an environment where I would not have dreamt of the possibility of getting any private money, any actual investment, in something that far out, that far ahead of its time, and he did it, again and again. It's insane what he managed to do.
What about someone like Elon Musk?
Sure, he's another one. He is totally impervious to the caution and criticism and conservatism that pervades humanity, and he's getting on making these bloody self-driving cars, space tourism, and so on, making them happen. He's thinking just the way I'm thinking really.
"You can just choose how frequently and how thoroughly you repair the damage. And you can make a different choice next time."
You famously said ten years ago that you think the first person to live to 1000 is already alive. Do you think that's still the case?
Definitely, yeah. I can't see how it could not be. Again, it's a probabilistic thing. I said there's at least a 10 percent chance that we won't get to what I call Longevity Escape Velocity for 100 years and if that's true, then the statement about 1000 years being alive already is not going to be the case. But for sure, I believe that the beneficiaries of what we may as well call SENS 1.0, the point where we get to LEV, those people are exceptionally unlikely ever to suffer from any kind of ill health correlated with their age. Because we will never fall below Longevity Escape Velocity once we attain it.
Could someone who was just born today expect—
I would say people in middle age now have a fair chance. Remember – a 50/50 chance of getting to LEV within 20 years, and when you get there, you don't just stay at biologically 70 or 80, you are rejuvenated back to biologically 30 or 40 and you stay there, so your risk of death each year is not related to how long ago you were born, it's the same as a young adult. Today, that's less than 1 in 1000 per year, and that number is going to go down as we get self-driving cars and all that, so actually 1000 is a very conservative number.
So you would be able to choose what age you wanted to go back to?
Oh sure, of course, it's just like a car. What you're doing is you're repairing damage, and the damage is still being created by the body's metabolism, so you can just choose how frequently and how thoroughly you repair the damage. And you can make a different choice next time.
What would be your perfect age?
I have no idea. That's something I don't have an opinion about, because I could change it whenever I like.
Residents of Fountain Hills, a small town near Phoenix, Arizona, fought against the night sky pollution to restore their Milky Way skies.
Light pollution is defined as the excessive or wasteful use of artificial light.
Light-emitting diodes (LEDs) -- which became commercially available in 2002 and rapidly gained popularity in offices, schools, and hospitals when their price dropped six years later — inadvertently fueled the surge in light pollution. As traditional light sources like halogen, fluorescent, mercury, and sodium vapor lamps have been phased out or banned, LEDs became the main source of lighting globally in 2019. Switching to LEDs has been lauded as a win-win decision. Not only are they cheap but they also consume a fraction of electricity compared to their traditional counterparts.
But as cheap LED installations became omnipresent, they increased light pollution. “People have been installing LEDs thinking they are making a positive change for the environment. But LEDs are a lot brighter than traditional light sources,” explains Ashley Wilson, director of conservation at the International Dark-Sky Association (IDA). “Despite being energy-efficient, they are increasing our energy consumption. No one expected this kind of backlash from switching to LEDs.”
Light pollution impacts the circadian rhythms of all living beings — the natural internal process that regulates the sleep–wake cycle.
Currently, more than 80 percent of the world lives under light-polluted skies. In the U.S. and Europe, that figure is above 99 percent.
According to the IDA, $3 billion worth of electricity is lost to skyglow every year in the U.S. alone — thanks to unnecessary and poorly designed outdoor lighting installations. Worse, the resulting light pollution has insidious impacts on humans and wildlife — in more ways than one.
Disrupting the brain’s clock
Light pollution impacts the circadian rhythms of all living beings—the natural internal process that regulates the sleep–wake cycle. Humans and other mammals have neurons in their retina called intrinsically photosensitive retinal ganglion cells (ipRGCs). These cells collect information about the visual world and directly influence the brain’s biological clock in the hypothalamus.
The ipRGCs are particularly sensitive to the blue light that LEDs emit at high levels, resulting in suppression of melatonin, a hormone that helps us sleep. A 2020 JAMA Psychiatry study detailed how teenagers who lived in areas with bright outdoor lighting at night went to bed late and slept less, which made them more prone to mood disorders and anxiety.
“Many people are skeptical when they are told something as ubiquitous as lights could have such profound impacts on public health,” says Gena Glickman, director of the Chronobiology, Light and Sleep Lab at Uniformed Services University. “But when the clock in our brains gets exposed to blue light at nighttime, it could result in a lot of negative consequences like impaired cognitive function and neuro-endocrine disturbances.”
In the last 12 years, several studies indicated that light pollution exposure is associated with obesity and diabetes in humans and animals alike. While researchers are still trying to understand the exact underlying mechanisms, they found that even one night of too much light exposure could negatively affect the metabolic system. Studies have linked light pollution to a higher risk of hormone-sensitive cancers like breast and prostate cancer. A 2017 study found that female nurses exposed to light pollution have a 14 percent higher risk of breast cancer. The World Health Organization (WHO) identified long-term night shiftwork as a probable cause of cancer.
“We ignore our biological need for a natural light and dark cycle. Our patterns of light exposure have consequently become different from what nature intended,” explains Glickman.
Circadian lighting systems, designed to match individuals’ circadian rhythms, might help. The Lighting Research Center at Rensselaer Polytechnic Institute developed LED light systems that mimic natural lighting fluxes, required for better sleep. In the morning the lights shine brightly as does the sun. After sunset, the system dims, once again mimicking nature, which boosts melatonin production. It can even be programmed to increase blue light indoors when clouds block sunlight’s path through windows. Studies have shown that such systems might help reduce sleep fragmentation and cognitive decline. People who spend most of their day indoors can benefit from such circadian mimics.
When Diane Turnshek moved to Pittsburgh, she found it almost impossible to see a clear night sky because the city’s countless lights created a bright dome of light called skyglow.
Diane Turnshek
Leading to better LEDs
Light pollution disrupts the travels of millions of migratory birds that begin their long-distance journeys after sunset but end up entrapped within the sky glow of cities, becoming disoriented. A 2017 study in Nature found that nocturnal pollinators like bees, moths, fireflies and bats visit 62 percent fewer plants in areas with artificial lights compared to dark areas.
“On an evolutionary timescale, LEDs have triggered huge changes in the Earth’s environment within a relative blink of an eye,” says Wilson, the director of IDA. “Plants and animals cannot adapt so fast. They have to fight to survive with their existing traits and abilities.”
But not all types of LEDs are inherently bad -- it all comes down to how much blue light they emit. During the day, the sun emits blue light waves. By sunset, red and orange light waves become predominant, stimulating melatonin production. LED’s artificial blue light, when shining at night, disrupts that. For some unknown reason, there are more bluer color LEDs made and sold.
“Communities install blue color temperature LEDs rather than redder color temperature LEDs because more of the blue ones are made; they are the status quo on the market,” says Michelle Wooten, an assistant professor of astronomy at the University of Alabama at Birmingham.
Most artificial outdoor light produced is wasted as human eyes do not use them to navigate their surroundings.
While astronomers and the IDA have been educating LED manufacturers about these nuances, policymakers struggle to keep up with the growing industry. But there are things they can do—such as requiring LEDs to include dimmers. “Most LED installations can be dimmed down. We need to make the dimmable drivers a mandatory requirement while selling LED lighting,” says Nancy Clanton, a lighting engineer, designer, and dark sky advocate.
Some lighting companies have been developing more sophisticated LED lights that help support melatonin production. Lighting engineers at Crossroads LLC and Nichia Corporation have been working on creating LEDs that produce more light in the red range. “We live in a wonderful age of technology that has given us these new LED designs which cut out blue wavelengths entirely for dark-sky friendly lighting purposes,” says Wooten.
Dimming the lights to see better
The IDA and advocates like Turnshek propose that communities turn off unnecessary outdoor lights. According to the Department of Energy, 99 percent of artificial outdoor light produced is wasted as human eyes do not use them to navigate their surroundings.
In recent years, major cities like Chicago, Austin, and Philadelphia adopted the “Lights Out” initiative encouraging communities to turn off unnecessary lights during birds’ peak migration seasons for 10 days at a time. “This poses an important question: if people can live without some lights for 10 days, why can’t they keep them turned off all year round,” says Wilson.
Most communities globally believe that keeping bright outdoor lights on all night increases security and prevents crime. But in her studies of street lights’ brightness levels in different parts of the US — from Alaska to California to Washington — Clanton found that people felt safe and could see clearly even at low or dim lighting levels.
Clanton and colleagues installed LEDs in a Seattle suburb that provided only 25 percent of lighting levels compared to what they used previously. The residents reported far better visibility because the new LEDs did not produce glare. “Visual contrast matters a lot more than lighting levels,” Clanton says. Additionally, motion sensor LEDs for outdoor lighting can go a long way in reducing light pollution.
Flipping a switch to preserve starry nights
Clanton has helped draft laws to reduce light pollution in at least 17 U.S. states. However, poor awareness of light pollution led to inadequate enforcement of these laws. Also, getting thousands of counties and municipalities within any state to comply with these regulations is a Herculean task, Turnshek points out.
Fountain Hills, a small town near Phoenix, Arizona, has rid itself of light pollution since 2018, thanks to the community's efforts to preserve dark skies.
Until LEDs became mainstream, Fountain Hills enjoyed starry skies despite its proximity to Phoenix. A mountain surrounding the town blocks most of the skyglow from the city.
“Light pollution became an issue in Fountain Hills over the years because we were not taking new LED technologies into account. Our town’s lighting code was antiquated and out-of-date,” says Vicky Derksen, a resident who is also a part of the Fountain Hills Dark Sky Association founded in 2017. “To preserve dark skies, we had to work with the entire town to update the local lighting code and convince residents to follow responsible outdoor lighting practices.”
Derksen and her team first tackled light pollution in the town center which has a faux fountain in the middle of a lake. “The iconic centerpiece, from which Fountain Hills got its name, had the wrong types of lighting fixtures, which created a lot of glare,” adds Derksen. They then replaced several other municipal lighting fixtures with dark-sky-friendly LEDs.
The results were awe-inspiring. After a long time, residents could see the Milky Way with crystal clear clarity. Star-gazing activities made a strong comeback across the town. But keeping light pollution low requires constant work.
Derksen and other residents regularly measure artificial light levels in
Fountain Hills. Currently, the only major source of light pollution is from extremely bright, illuminated signs which local businesses had installed in different parts of the town. While Derksen says it is an uphill battle to educate local businesses about light pollution, Fountain Hills residents are determined to protect their dark skies.
“When a river gets polluted, it can take several years before clean-up efforts see any tangible results,” says Derksen. “But the effects are immediate when you work toward reducing light pollution. All it requires is flipping a switch.”