What If We Never Age?

What would it cost to live forever? In this episode of The Active Share, Hugo is joined by Dr. Greg Bailey, co-founder and executive chairman of Juvenescence, for an in-depth discussion about the science of aging, the societal and economic impacts of extended lifespans, and how advancements in biotech are paving the way for longer, and healthier, lives.

Comments are edited excerpts from our podcast, which you can listen to in full below.

You began your career as a physician and are now a biotech entrepreneur tackling the challenge of aging. Can you share how that journey unfolded?

Dr. Greg Bailey: I’ve always had an entrepreneurial spirit. In emergency medicine, you’re only allowed to work a certain number of hours per week. But after graduating medical school, I was a workaholic. I began looking at other opportunities and eventually came to work on two biotech ventures.

My personal journey began when I met Luigi Fontana, one of the top doctors in the world for caloric restriction. Under caloric restriction, he believes men should consume only 1,800 calories and women 1,200 calories.

During the following year, I was at an event where Valter Longo, a biogerontologist and cell biologist known for his studies on the role of fasting, presented. He said that a person should “reset” their body by only consuming 800 calories for five straight days once every month if they’re overweight and once every three months if they’re a normal weight.

The scientists I work with at Juvenescence theorize that this tricks your body into thinking it's going into a fasting state. It begins to process energy in a different way, which spurs an engine in your cell called the mitochondria. This process has a similar effect to caloric restriction and has become well known under the name ProLon.

I then talked to Peter Attia. We discussed dieting and how the human body turns insulin-resistant around 45 to 50 years of age. Organs can no longer properly process sugar, causing sugar levels in your brain, heart, and muscles to increase. At that time, we hypothesized that that may be type 3 diabetes and could lead to one of the forms of Alzheimer's disease.

I also spoke with Walter Bortz, the head of gerontology at Stanford. He said that if you're a fit person, you mentally and physically decline at half a percent a year. But if you’re unfit, the rate of decline jumps to two percent a year.

Scientists are beginning to understand the pathways that cause our cells to age. And one thing I know about scientists is if they can see the pathways, they will figure out how to tinker with them.

So, it almost felt like a responsibility. I thought, “This nascent industry could struggle for credibility and to raise money. And it will take time getting funding and attracting the right people.” My partners and I wanted to change the health trajectory of the world.

If someone excels in fitness, is that enough to ensure a long and healthy life?

Dr. Bailey: Lifestyle is a big factor. If a person’s blood pressure is under control, and they don’t smoke, have good nutrition, and have a good sleep schedule, then they will start at a higher point on the aging curve.

We’re beginning to understand why a human body declines, what pathways are involved, and how to modify those pathways. But to live until 120 or 150 years old and still be healthy will take much more than exercise and nutrition.

And if we want to solve aging, we also must find a cure for Alzheimer's. Nobody wants to live to 150 if they can’t remember the last 60 years of their life. Thus, Juvenescence is trying to address tissue regeneration and the slowdown of cellular aging. Our scientists were able to cut off the limb of a frog and regrow it and have begun to experiment on a mouse.

Science fiction is becoming science, and that’s extraordinary.

If we want to solve aging, we also must find a cure for Alzheimer's. Nobody wants to live to 150 if they can’t remember the last 60 years of their life.

Why do we age?

Dr. Bailey: Things just change within a person’s body. We lose the ability to clear toxic materials as we get older. I mentioned the mitochondria—once the engine of a cell begins to falter, DNA will begin to fracture. That’s called autophagy.

I like to think of it this way: if you have a fireplace in your house, but you don't clean the chimney, eventually it will close with the more logs you burn, and the fireplace will cease to work.

So, as your cells begin to use energy, they create a negative reaction. Cells clear up well when you're young but cease to clear as well as you get older. The chimney is beginning to close, so to speak.

There’s also nicotinamide adenine dinucleotide (NAD), a coenzyme central to metabolism that decreases as you age and is part of the energy cycle for the cell. People have tried to take NAD to boost their cells, but it isn’t an easy process.

Part of the reason NAD declines with age is because of an enzyme called Cluster of Differentiation 38 (CD38), which increases with age. It destroys NAD. Taking NAD without modifying the CD38 pathway is like trying to fill a bathtub with the drain open.

What kind of products are in development that address these issues?

Dr. Bailey: There's an institute called the Buck Institute, where 200 of the top scientists in the world are working to solve aging. They created a product that is a CD38 inhibitor. By this time next year, we will have that in human trials, as well as trying and modifying NAD.

This is fascinating because what we try to do at Juvenescence is bring a person back to a 35- to 40-year-old physiological level. By decreasing the CD38 enzyme, we hopefully can find the right level for your cells.

There’s also the Klotho gene that plays a key role in regulating aging and longevity; it produces a protein that acts as a hormone and has been shown to extend lifespan in animal studies when overexpressed.

How close are we to developing drugs that can tackle the fundamental issues of aging?

Dr. Bailey: Right now, there is a drug called rapamycin that is being tested as an anti-aging drug. It has a pathway called mammalian target of rapamycin (mTOR), which is one of the four major pathways involved in aging.

Rapamycin is influencing the pathway that's now named after it. But conceivably, it could be an anti-aging drug that we have today. Several of the top scientists in this sector are studying this drug for anti-aging properties.

The problem is we haven't done a proper clinical trial. But some very good research has been done on dogs by Matt Kaeberlein, an American biologist studying aging, at Washington University. The regimen was 6 milligrams once a week for 10 weeks, then a three-month break. The cycle then repeats.

However, there’s already an anti-aging drug on the market: Ozempic. Glucagon-like peptide-1 (GLP-1) receptor agonists help increase how long people live by decreasing diseases common in overweight people.

Gerald I. Shulman, Ph.D., a professor of medicine and cellular and molecular physiology at Yale, tested 21- to 22-year-old Yale students, all slim and in reasonably good shape, and found that 25% of them were already insulin-resistant. Sugar was already beginning to damage their organs.

But to truly solve aging will be complicated and may need quantum computing. Artificial intelligence (AI) will likely be very helpful in drug discovery when it comes to pattern recognition, as it can look at 20 million things in a nanosecond. That would take a person years to try to find interesting-looking chemical compounds.

Science fiction is becoming science, and that’s extraordinary.

Is AI transforming our understanding of aging pathways?

Dr. Bailey: The more we understand aging pathways, the better equipped scientists are to study them. DNA uses RNA to create proteins, which act as messengers on a cellular level, ultimately producing metabolites.

While we have mapped many genes and identified most proteins, metabolites remain a largely unexplored area—but they could be critically important.

With millions of metabolites to analyze, AI will be essential to sort through them and help rebalance the four key cellular pathways: mTOR, NAD, the adenosine monophosphate-activated protein kinase (AMPK) enzyme, and sirtuin, a kind of protein involved in the aging process. These pathways operate in a feedback loop, and finding the right balance will likely vary for everyone. It will require personalized approaches to treatment.

Another major opportunity, which isn’t being discussed enough, is using AI in clinical trials. AI could potentially identify a 99% likelihood of a drug's success within just one month by recognizing patterns that humans can't see.

This would not only accelerate the development of effective treatments but also significantly reduce costs, making drugs more affordable.

Are we entering a technologically enabled golden age?

Dr. Bailey: Back in 2000, Macquarie Asset Management said that medical knowledge was doubling every five years. In 2010, they said it was every three-and-a-half years. In 2020, they said it was every 73 days. Because of the enormous amount of money that came in during COVID, I think we’re entering a golden age.

Since stepping down as the CEO of Juvenescence, I have developed three pillars to live by: pass on the knowledge I've learned from the top scientists in the world; convince payers, whether it's national healthcare services or insurance companies, that we must change from our current model of sick care; and convince people that they can invest in biotech.

If people are willing to take just 1% of their net worth and dedicate it to biotech, we could have an extraordinary renaissance.

Are regulators ready for this golden age?

Dr. Bailey: Regulation is crucial, but sometimes regulators can be overzealous. There will need to be an education process for regulatory bodies to trust AI in areas like clinical trials.

A major challenge for regulators is that we can’t run 75-year clinical trials on anti-aging drugs. Instead, we need biomarker panels to measure aging more efficiently. For example, in 2018, Greg Fahy and Steven Horvath at UCLA used DNA methylation as a biomarker. They tested two drugs and three supplements over two years and showed that participants’ biological age dropped by two years during just one year of treatment.

If we could consistently repeat this result, we might achieve what’s called “escape velocity,” where we slow aging faster than we age. While this is a simplification, it highlights the exciting possibilities in anti-aging research, even as we confront the question of whether cells can surpass a lifespan of 150 years.

With millions of metabolites to analyze, AI will be essential to sort through them and help rebalance the four key cellular pathways.

If people live longer, and they're healthier for longer, can they remain productive?

Dr. Bailey: Harvard did a study that found if we all live to 150 years old, it could increase the population by 3% by the end of the century. But we have an inverted demographic pyramid—there are not enough young people to support the elderly, which could result in the next major economic crisis.

However, if a still-healthy 85-year-old can continue to participate in society, then it changes everything. Interestingly, the difference between healthspan and lifespan in the developed world is 10 years (except in Denmark, where it's three years). Wouldn't it be great if it were one year, one week, or one day?

That’s the goal. When my partners and I began Juvenescence, we were asked what we were trying to do. And we said, “We want to add 10 healthy years to a person’s life.” If we do that, we could give everyone an extra day of the week. It's that profound, and the economic consequences are huge.

What should an ideal daily health regimen look like?

Dr. Bailey: First, find a fitness routine you enjoy. Ideally, it should include a mix of yoga, Pilates, endurance training, weight training, and high-intensity workouts. Even gardening can work.

Nutrition is the next priority. The Mediterranean diet is great for most people in Europe and North America, but nutrition has an ethnocentric element. For example, if we ate as much white rice as the Japanese, we'd likely develop diabetes.

I also recommend eating as many fruits and vegetables as possible and aiming for seven to eight hours of sleep per night.

Personally, I eat 10 to 12 servings of vegetables and 3 to 5 servings of fruit daily, with a focus on neuroprotective foods like spinach, broccoli, cauliflower, and blueberries. I spread my protein intake throughout the day instead of consuming it all in one sitting and make sure to get eight hours of sleep, maintain a mix of exercise, and take supplements that I've carefully vetted with scientists.