Entrepreneur Dave Aspreys end-of-life plans are quite simple, really, even if some of his ambitions sound laughably optimistic to most of us.I want to die at a time and by a method of my own choosing, and keep doing awesome things until that day, he tells me. I dont think its outrageous to believe Ill make it to 180 years old. And if I run out of energy, itll just be because I did too much cool shit for my own good.

Asprey is strolling across his lush property in British Columbia, holding up his phone and pointing out the specimens in this years garden as we chat over Zoom in the midst of the global pandemic. Hes protecting his skin from the sun with a goofy Outdoor Research hat and wearing a long string of beads that he says are each over a hundred years old, from cultures around the world.

Asprey, 48, is the founder of the Bulletproof wellness empire and a vocal champion of the movement to extend human life expectancy beyond 100 years. Hes made millions by experimenting on his own body and packaging his home-brewed discoveries into books, a podcast, consulting services and consumer products (you may have even tried his butter-laced coffee). Asprey, who was a web-security executive before he became the Bulletproof Executive, is just one of a cadre of tech elite who have begun directing their attentionand truckloads of moneytoward the problem of life extension. Jeff Bezos, Peter Thiel, Sergey Brin, Larry Ellisonname a Silicon Valley A-lister and he or she is likely funding longevity research, experimenting with anti-aging interventions or both. These are the masters of the universe who see no reason they cant take the tech industrys optimization obsession and apply it to the ultimate challenge: conquering death itself.

And their efforts appear to be paying off: Thanks to a recent explosion of advances in longevity medicine, Aspreys vision of living healthfully into his second century might not be so crazy. In fact, for people in middle age right now, a handful of therapies in clinical trials have the potential, for the first time in human history, to radically transform what old age looks like. If the life extensionists are right, a person whos 40 today might reasonably expect to still be downhill skiing, running a 10K or playing singles tennis at 100.

Dave AspreyDave Asprey

If you do anti-aging right, Asprey insists, youll have a level of resilience and energy to fight what comes your way. If you get Covid-19, youre less likely to become very sick. The idea is that at a cellular level, youre making yourself very hard to kill.

The most extreme of the controversial interventions Asprey has undergone involved having stem cells extracted from his own bone marrow and fat and then injected into hundreds of locations on his body. Into every joint, between every vertebra and into my cerebrospinal fluid, face and sex organs, he tells me cheerfully. For what I spent on that, I could have bought a really nicely appointed Tesla.

He trots up a flight of stairs to his home office, which sits above a million-dollar lab filled with health gadgets, such as a cryochamber, a hypoxic trainer and an AI-enabled stationary bike. For a wealthy person, investing in your body should be a major part of your Im rich strategy, he explains. Personally, I think you should be spending at least 2 to 3 percent of your net worth on health and longevity. Get a personal chef who can cook you the right food. Its not that hard.

It might be an exaggeration to say BioViva CEO Liz Parrish believes death is optional, but for her, Aspreys goal of living to 180 shows a distinct lack of ambition. If you can reach homeostasis in the body, Parrish says, where its regenerating itself just a little bit faster than its degrading, then what do you die of? An accident or natural disaster, probably. Theres no expiration date at 90 or 100 years old.

Tall, blond and fit, Parrish cuts a strikingly youthful figure at 49one that might convince you to order whatever shes having. But, like Asprey, she has received criticism from the longevity research community for becoming patient zero in her own experimental drug trial, aimed at halting aging at the cellular level. In 2015, Parrish underwent telomerase and follistatin gene therapies in Bogota, Colombia. The procedures involved receiving around a hundred injections of a cocktail of genes and a virus modified to deliver those new genes into her bodys cells. The objective was to prevent age-related muscle loss and lengthen her telomeres: the caps at the end of our chromosomes. Scientists have identified their unraveling as not only a marker of aging but also a potential cause of age-related decline.

Liz ParrishLiz Parrish

Parrish told the media about her clandestine experiment and has published periodic updates on her condition in the five years since, and she reports that she has indeed increased her muscle mass and lengthened her telomeres. Parrishs punk-rock approach stems from her conviction that the medical-research communityboth the Food and Drug Administration (FDA) and researchers who arent business-mindedis moving too slowly, with too much red tape, when it comes to advancing aging therapeutics. But gene therapy is a relatively new area of medicine that brings with it a host of new risks, including cancer, severe immune reactions and infections caused by the viral vector used to deliver the drug.

Parrish downplays such worries. There may be risks, she tells Robb Report. But the known risk is that youre 100 percent likely to die. So you have to decide for yourself if the potential benefit outweighs that.

Humans have always aspired to find the fountain of youth, so people might be skeptical about the fact that anti-aging technologies are working now, says British investor and businessman Jim Mellon. But the fact is that this is finally happening, and we need to seize the moment. Mellon cofounded Juvenescence, a three-year-old pharmaceutical company thats investing in multiple technologies simultaneously to increase the odds of bringing winning products to market.

Mellon, 63, has made his fortune betting on well-timed investment opportunities, and he predicts that a new stock-market mania for life extension is just around the corner. This is like the internet dial-up phase of longevity biotech, he enthuses. If youd invested in the internet in the very early days, youd be one of the richest people on the planet. Were at that stage now, so the opportunity for investors is huge. According to a report by Bank of America Merrill Lynch, hes not wrong: The market for technologies to increase human life span is projected to grow sixfold to $610 billion in just the next five years.

When I talk to Mellon in the late spring, hes sequestered on the rugged coast of the Isle of Man, a tiny spit of land in the Irish Sea. Despite being what he describes as imprisoned there for 15 weeksand countingduring the Covid-19 shutdown, hes jovial and chatty and wants to make it clear that his interest in life extension is much more than financial. Working to extend life is an ethical cause, he says. If we can help people to live healthfully until the end of life, well transform the world completely. Well reduce a huge amount of pressure on failing health-care systems, and well have to reimagine pension and life insurance. This should be the number-one tick in anyones investment portfolio.

If youd like to get on board with this social-impact view of longevity, it helps to understand the trajectory of aging today. In Americas most affluent neighborhoods, the average life span is about 88 years. (Meanwhile, in this countrys poorest, it hovers around a meager 66 because of a raft of inequalities, such as diet, stress, smoking, pollution and health care.) For most people, health starts gradually diminishing in the last 15 years of life with the onset of chronic conditions, including arthritis, neurodegeneration and diabetes. If we could eliminate such diseases of aging, experts say, the US could save an estimated $7.1 trillion in health-care costs over the next 50 years. (Quite where all these sprightly centenarians might live on this already densely populated planet remains to be seen.)

Jim MellonEric Verdin

One of Mellons bets is on a class of drugs called senolytics, which destroy senescent cells: the so-called zombie cells that, for complex reasons, stop dividing as we age. Senescent cells harm the body by secreting compounds that cause inflammation in surrounding tissues. Many age-related conditionsarthritis, diabetes, Alzheimers, cancerhave an inflammatory component, and studies suggest that a buildup of senescent cells is a large part of the problem.

A number of biotech start-ups are devel- oping drugs that target cell senescence, but the furthest along is Unity Biotechnology, a company in South San Francisco that has three drugs in clinical trials to address aging conditions, starting with osteoar- thritis of the knee. Unity raised more than $200 million from such big names as Thiel and Bezos, who chipped in through their investment firms, before going public in 2018. Since then, Mellon has also bought a small stake.

The holy grail of senolytics will be the development of a preventive therapy to wipe out senescent cells in the body before they cause conditions of aging, theoretically extending life span. In June, a team from Sloan Kettering published new breakthrough research showing that CAR T cellstypically used for precision cancer therapycan also be used to target and kill senescent cells. Prescription senolytics for anti-aging therapy are still years away, but unsurprisingly, theres an audience of longevity enthusiasts who want to access such anti-aging miracles yesterdayand no shortage of FDA-unapproved ways to chase after them. For instance, after a few studies examined the senolytic effects of a chemotherapy drug called dasatinib, the website FightAging.org published a step-by-step guide to senolytic self-experimentation using chemotherapeutics.

It doesnt take a Ph.D. in biochemistry to guess that taking off-label chemo drugs might come with harmful side effects, but that hasnt stopped a zealous group of body-hackers from trying it themselves and chronicling their efforts online. The internet is littered with novice longevity adviceand sketchy anti-aging companies eager to separate the hopeful and desperate from their money, like the company that charges $8,000 for transfusions of plasma from the blood of teenagers and early-twentysomethings (yes, just like Gavin Belson on HBOs Silicon Valley). Many of these are at best ineffective and at worst deadly, since the same cellular systems that fuel growth in young people might cause cancer when tipped into overdrive. Imagine the tragic irony of paying tens of thousands for a therapy that promises to help you live longer but actually causes the cancer that kills you.

Adobe

Beyond the obvious red flags of repurposed chemo drugs and the bloodletting of teens, it can be difficult for a layperson to separate the world-changing longevity breakthroughs from the terrible ideas. Enter one of the worlds leading experts on longevity to help make sense of things.

Eric Verdin, 63, is president and CEO of the Buck Institute, a globally renowned center for aging research just outside San Francisco in Marin County. Verdin is bullish on the promise of living healthfully to at least 100. Today. But 180? Dont count on it. My prediction, based on everything we know today, is that getting to 120 is about the best we can do for the foreseeable future. Ill bet my house were not going to see anyone live to 180 for another 200 years, if ever, he says. But making everyone a healthy centenarian, this is something we can do today. And thats something to be excited about.

Verdins own lab at the Buck Institute studies the aging immune system and how its affected by lifestyle factors, such as nutrition and exercise. Informed by this research, Verdin follows a time-restricted diet in which he eats all of his meals in an eight-to-nine-hour window (similar to the Buchinger Wilhelmi process) and gets plenty of exercise mountain biking in Marins steep hills. The good news is that over 90 percent of what causes diseases of aging is environmental, and that means its within your control, he says.

But he emphasizes that responsible management of your health comes with limits, like avoiding experimental therapies. A group of people have decided to try some expensive and dangerous interventions, but there is zero evidence that any of these are going to help them live longer, he says. The problem, according to Verdin, is that the results of aging interventions in mouse trials can look very promising but rarely translate to success in humans. Theres a huge delta between the health of a stressed lab mouse and an optimally healthy mouse, Verdin says. So when you treat lab mice with longevity therapeutics, you see an outsized result that doesnt at all guarantee the same result in humans.

On the other hand, Verdin tells Robb Report, there are definitely new protocols worth getting excited about. Take, for instance, rapalogs, a class of drugs that interact with a protein called mTOR, which serves as a linchpin for multiple critical biological processes, including cell growth and metabolism. Rapalog drugs tamp down mTOR, possibly preventing age-related diseases such as diabetes, stroke and some cancers. The drug rapamycin, the most heavily studied formula, was approved in the US in 1999 to help prevent organ-transplant rejection. Last year the medical journal Aging published a rapturous opinion piece by oncologist Mikhail Blagosklonny in which he made the case that rapamycinin small or intermittent dosesis effective as a preventive treatment to ward off diseases of aging, and that, in the elderly, not taking rapamycin may be even more dangerous than smoking.

Eric VerdinJim Hughes Photography

Later this year, a biotech firm called resTORbio, which was spun out of the Swiss-based Big Pharma company Novartis in 2017, is expected to seek FDA approval for its rapalog RTB101, which clinical trials have shown to slow age-related decline of the immune system and improve immune response in elderly people by more than 20 percent, a key factor in protecting vulnerable aging populations from disease. (It is currently in trials on elderly patients with Covid-19.) This is the furthest-along program of anything in the aging field, Joan Mannick, cofounder and chief medical officer of resTORbio, told MIT Technology Review last year. If health authorities approve this drug well have a product for people to prevent age-related diseases. Not just in our lifetime, but in, you know, a few years.

One of the many effects of rapamycin is that it mimics the mechanisms of calorie restriction. As Verdins lab and others have shown, fasting provides a number of anti-aging benefits, including insulin regulation, reduced inflammation and, to put it colloquially, clearing out the gunky by-products of metabolismpart of the reason Twitter CEO Jack Dorsey and other tech titans eat just a few meals per week. For lesser mortals, fasting is extremely hard to commit to and not much fun, hence the huge interest in calorie-restriction mimetics like rapamycin, which provide all the benefits without the downer not-eating part.

Of all the calorie-restriction mimetics, the one sparking the most excitement among longevity researchers is already on the market: metformin, a decades-old diabetes drug. Metformin became a part of the Silicon Valley health regimen several years ago after an epidemiological study showed that Type 2 diabetics who took the drug lived longer than non-diabetics who didnt. Just about everyone in the longevity industry takes metformin, Verdin tells me. He takes it himself, and nearly everybody I interviewed is taking or has taken it, too.

In April, Nir Barzilai, the renowned endocrinologist who spearheaded research on the anti-aging properties of metformin, announced in an opinion piece he co-authored in the journal Cell Metabolism that his lab is launching a large clinical trial to investigate the anti-aging effects of the drug on non-diabetic populations. Barzilais goal is to prove to the FDA that aging itselfrather than conditions associated with it, like Alzheimers and arthritiscan be targeted as a disease. If Barzilai is successful and the FDA approves aging as a treatment indication, the process of bringing longevity therapies to market would accelerate rapidly.

Just as the FDA was able to move faster to bring Covid-19 therapies to market this year, we will reach a tipping point when public opinion pushes the FDA to approve aging as an indication, and the longevity-research field will make leaps as a result, Mellon says. He has contributed funding to Barzilais metformin research, which he believes will be instrumental in proving that there are compounds that can extend human life across the board.

The fact of the matter is that the US has the best regulatory system for new drug development in the world, Mellon says. Were in the first era ever when humans can be bioengineered to live longer. And in 10 years, well have solutions that are even better than today. Just wait, its coming.

Liz Parrish

Jim Mellon

Diet:Vegetarian.Mindfulness practice:Nightly meditation.

Exercise regimen:30 minutes of cardio and 10 minutes of weights,five days a week.

Anti-aging Rx:Regenerative gene therapies. Im certain most peoplewill take them in the next couple decades.

180th-birthday wish:Solving another critical issue.

Sleep routine:7.5 hours plus a 30-minute nap; in bed by 9 p.m.

Vitamins/supplements/ prescription meds:Vitamins D and B12, metformin.

Exercise regimen:Walk or run minimum 10,000 steps a day;weights three times week.

Anti-aging Rx:Green tea.

100th-birthday wish:Another 25 years.

Dave Asprey

Jim Hughes Photography

180th-birthday wish:Either a cruise to Mars or a 1970 Mustang Fastback,which by then will be 210 years old!

Sleep Routine:Avoid: coffee after 2 p.m., heavy workouts after 6 p.m.,alcohol during the week and heavy eating in the evening.

Vitamins/supplements:Vitamin D, omega fatty acids, NMN, citrus bioflavonoidcomplex, fiber supplement, prebiotic supplement.

Diet:Fasting-mimicking diet once every four to six months;roughly 16:8 intermittent fasting at other times.

Mindfulness practice:Daily meditation.

Anti-aging Rx:I love cooking and eating, so I do not restrict foodon the weekend. Happiness with friends and family is thesurest path to longevity.

100th-birthday wish:A bike tour across the US, from coast to coast.

Link:
Why Silicon Valley Execs Are Investing Billions to Stay Young - Robb Report

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