Isabella Connelley and Bethan Mooney for TIMEIsabella Connelley and Bethan Mooney for TIME

The titans of the tech industry are known for their confidence that they can solve any problem--even, as it turns out, the one that's defeated every other attempt so far. That's why the most far-out strategies to cheat death are being tested in America's playground for the young, deep-pocketed and brilliant: Silicon Valley.

Larry Ellison, the co-founder of Oracle, has given more than $330 million to research about aging and age-related diseases. Alphabet CEO and co-founder Larry Page launched Calico, a research company that targets ways to improve the human lifespan. Peter Thiel, co-founder of PayPal , has also invested millions in the cause, including over $7 million to the Methuselah Foundation, a nonprofit focused on life-extension therapies.

Rather than wait years for treatments to be approved by federal officials, many of them are testing ways to modify human biology that fall somewhere on the spectrum between science and entrepreneurialism. It's called biohacking, and it's one of the biggest things happening in the Bay Area.

"My goal is to live beyond 180 years," says Dave Asprey, CEO of the supplement company Bulletproof, most famous for its popularization of coffee with organic butter mixed in. "I am doing every single thing I can to make it happen for myself."

For some, that means daily pill regimens and fasting once a week. For others, it means having the blood of a young person pumped into their veins. "I see biohacking as a populist movement within health care," says Geoffrey Woo, the CEO of a company called Nootrobox that sells supplements that promise to enhance brain function.

Many scientists are skeptical. Here's what's known--and what isn't--about the latest front of humanity's fight against the inevitable.

THE HACK: It may sound vampiresque, but 50 people in the U.S. have paid $8,000 for a transfusion of plasma from someone between the ages of 16 to 25. The study is run by Ambrosia, a company based in Monterey, Calif.

THE HYPE: The transfusions are based on the idea that two-liter injections of blood from the young may confer longevity benefits. Now, in the first known human clinical trial of its kind, Ambrosia is enlisting people willing to pay the hefty price to give it a shot.

Ambrosia's founder, Jesse Karmazin, who has a medical degree but is not a licensed physician, says that after the transfusions, his team looks for changes in the recipient's blood, including markers of inflammation, cholesterol and neuron growth. "When we are young, we produce a lot of factors that are important for cellular health," he says. "As we get older, we don't produce enough of these factors. Young blood gives your body a break to repair and regenerate itself."

THE DEBATE: Scientists are roundly critical of this study, in large part because of the way it has been designed: there's no control group, it's costly to participate in, and the people enrolled don't share key characteristics that make them appropriate candidates to be looked at side by side.

"What Ambrosia is doing is not useful and could be harmful," says Irina Conboy, an associate professor of bioengineering at the University of California, Berkeley, who is also studying blood as a potential target for aging.

The concept stems from mouse research by Conboy and others. In 2005, she and her research partner and husband Michael Conboy showed that when older mice were surgically sutured to younger mice, their tissues got healthier. The takeaway was not that young blood is a cure-all, but some entrepreneurs ran with the idea. "The story has switched into a highly exaggerated search of young blood as a silver bullet to combat aging," Irina says.

In a recent follow-up study, the Conboys developed a way to exchange the blood of young and old mice without surgically joining them. They found that old mice had some improvements but that young mice experienced rapid declines.

"The big result is that a single exchange hurts the young partner more than it helps the old partner," says Michael. Ambrosia says plasma transfusions are safe and, if proven effective, should be made available.

THE BOTTOM LINE: Blood-based therapies for longevity could still be in our future, but the science isn't there yet. "Donor blood can save lives, but using it to rejuvenate oneself is counterproductive," says Irina.

THE HACK: If you could learn your risks for the most-feared diseases years before you'd actually get sick, would you? For the curious (and the brave), there's Health Nucleus, an eight-hour, $25,000 head-to-toe, inside-and-out physical exam that includes whole-genome sequencing, high-tech scanning and early diagnostics. The goal is to paint a granular picture of an individual's health and disease risk, which could then inform lifestyle and medical choices that keep you healthier, longer.

THE HYPE: Health Nucleus bills the elite program as "a genomic-powered clinical research project that has the potential to transform health care." It was founded in 2015 by J. Craig Venter, the scientist widely credited with being one of the first to sequence the human genome, and it doesn't come cheap. The Health Nucleus price tag is for a single session, during which patients get a sequencing of their genome and microbiome, a full-body MRI and an array of blood tests. When the results come in, doctors translate the findings into measurements that patients can understand--and advice they can act upon.

The Health Nucleus team believes this deluge of information can help doctors flag problems that could lead to premature death for their patients down the line. "Right now medicine is a reactionary system where if you get pain or other symptoms, then you go see your doctor and they see if they can fix it," says Venter. "It's totally different from trying to predict your risk or identifying problems early, before they cause fatal disease. If you have the right knowledge, you can save your life."

THE DEBATE: Genome sequencing can indeed pinpoint genetic risk for some cancers and other diseases. And microbiome profiles--which look at the makeup of bacteria in the gut--can provide clues about the presence of some chronic diseases. Changes in cholesterol and blood sugar can also signal illness, though that kind of blood work is routinely tested by primary-care physicians.

About 400 people ages 30 to 95 have had the physical so far, and the test has identified significant medical problems in 40% of them, according to Venter, who says they've found cancer, aneurysms and heart disease in several people without symptoms.

Still, it raises questions among its skeptics about whether or not patients can actually use most (or any) of the data they receive. It also highlights some doctors' concerns about the negative consequences of overscreening, where there is always a risk for false positive results. "When healthy people undergo scanning, it can backfire," says Dr. Eric Topol, director of the Scripps Translational Science Institute, who has studied data-driven medicine. "It can find abnormalities and lead to more tests and procedures, many of them unnecessary. It can cause harm, not to mention anxiety and expense."

This isn't news to Venter. "The criticism people throw out is 'How dare you screen healthy people?'" he says. "My response is, 'How do you know they're healthy?' We are finding pretty good evidence that many are not."

Topol says a rigorous study of the program by independent researchers could help settle the score. "If validated for benefit in this way," Topol says, "my outlook would be more positive."

THE BOTTOM LINE: Venter acknowledges that while costs may come down, the battery of tests is so far too expensive to be realistic for most. Whether it adds years to a person's life is also an open question. For now, looking into the crystal ball requires a whole lot of money--and a comfort with uncertainty.

THE HACK: Biohackers in Silicon Valley and beyond have long experimented with the idea that a fistful of supplements, taken in just the right combination, may be the antidote to aging. Now, scientists and businesspeople are experimenting with the idea that just one or two pills, taken daily, may also get the job done.

THE HYPE: Many companies sell supplements with suspected longevity benefits, but one of the more talked-about new businesses is Elysium Health, co-founded by entrepreneurs and an MIT antiaging researcher named Leonard Guarente. Elysium has created a daily supplement, called Basis, that is "designed to support long-term well-being at the cellular level." The pill isn't marketed as a cure for aging, but Elysium Health cites evidence that the ingredients in the pill increase a compound called NAD+ that the company says is "essential to hundreds of biological processes that sustain human life." Basis costs $50 for a monthly supply, and the company, which doesn't release official sales numbers, says it has tens of thousands of customers so far.

THE DEBATE: Basis contains two main ingredients: nicotinamide riboside (NR) and pterostilbene, both of which have been shown in animal studies to fight aging at the cellular level. NR creates NAD+, which is believed to spur cell rejuvenation but which declines naturally in animals as they age. In a trial of 120 healthy people from ages 60 to 80, Guarente found that people taking Basis increased their NAD+ levels by 40%. "We are trying to be rigorously based on science," he says.

Studies have shown that supplementing with the compound extends life in mice, but whether it increases human longevity is unknown. To find out if it does--and to request FDA approval for the pill's clearance as a drug--long, rigorous clinical trials would need to be done. Instead, Elysium Health has released Basis as a supplement. That prevents the company from making specific medical claims about the pills--something that's prohibited by law in the marketing of supplements.

"I think the pathway Guarente is targeting is interesting"--meaning the idea that increasing NAD+ may also slow aging--"but clinical evidence is crucial," says Dr. Nir Barzilai, a researcher at Albert Einstein College of Medicine, who also studies drugs for aging.

Other scientists question the supplement approach altogether. "There is no evidence whatsoever that [Basis] produces health benefits in humans," says Dr. Jeffrey Flier, former dean of Harvard Medical School. "Many molecules that have some apparent benefits in mice or other organisms have no benefit when studied in humans."

The company has seven Nobel Prize--winning scientists on its advisory board, a fact that has also raised some eyebrows. Flier cautions that the company's association with lauded researchers cannot replace the science required to prove that the supplements combat aging and are safe to use.

THE BOTTOM LINE: It's too early to tell whether supplements can have any life-extending effects in humans.

THE HACK: These supplements, called nootropics or sometimes "smart drugs," promise to sharpen your thinking and enhance mental abilities. Many common nootropic ingredients--including the sleep-enhancing hormone melatonin, energy-boosting B vitamins as well as caffeine--are already present in the foods and pills that people consume on a daily basis.

THE HYPE: Nootrobox, one company that makes nootropics, combines ingredients like B vitamins and caffeine with a bouquet of other ingredients to create capsules with different purposes. "Rise" pills claim to enhance memory and stamina, "Sprint" pills promise an immediate boost of clarity and energy, "Kado-3" pills offer "daily protection of brain and body," and "Yawn" pills offer what you'd expect. A combo pack of 190 capsules retails for about $135.

Nootrobox is one of the more popular nootropic startups, with more than $2 million in funding from private investors like Yahoo CEO Marissa Mayer and the venture-capital firm Andreessen Horowitz. "I think nootropics will become things we consume on a daily basis," says the company's CEO, Geoffrey Woo.

THE DEBATE: The ingredients in nootropic supplements have a "generally recognized as safe," or GRAS, designation from the FDA, and some of them have been studied for their cognitive-enhancing effects. But the unique combinations in the pills themselves haven't been proven to heighten people's mental capacity. Nootrobox says it is currently conducting clinical trials of its products.

The FDA is notoriously hands-off when it comes to the regulation of dietary supplements. In the U.S., vitamins are not required to undergo rigorous testing for effectiveness or safety before they're sold.

Many doctors are also skeptical that they make a difference in mental performance. "There's probably a lot of placebo effect," says Kimberly Urban, a postdoctoral research fellow at the Children's Hospital of Philadelphia who has studied the effects of nootropics on the brain. "I think people should use some caution, especially young people." She adds that while these supplements may in fact be safe, there's no scientific research to prove it.

THE BOTTOM LINE: Many nootropics on the market are probably less sugary and lower in caffeine than most energy drinks, which often contain similar ingredients to those in the pills. Still, the notion that they make people sharper is largely unproven. So until independent clinical trials prove otherwise, it's buyer beware.

THE HACK: Calorie restriction--the practice of consuming nothing but water for a day at a time or drastically slashing calories a few days per week--has been popular for decades among eternal-youth seekers and health nuts alike. Now some companies are taking the guesswork out of it with fasting-diet meal-delivery kits.

THE HYPE: Not eating on a regular basis certainly sounds unpleasant, but proponents say that doing so comes with the benefits of better health, a stronger immune system and possibly even a longer life.

To help people get closer to this goal, L-Nutra, a Los Angeles--based company, offers a five-day, ultra-low-calorie meal kit called ProLon, which is designed to mimic fasting and promote health and longevity.

The meal kit includes energy bars, plant-based snacks, vegetable soups and algal-oil supplements that add up to a total of 770 to 1,100 calories a day. A five-day kit that must be ordered by a doctor costs $299.

THE DEBATE: Studies do show that calorie-restricted diets are linked to longer life expectancy. It's not clear why, exactly, but some scientists suspect that stressing the body kicks it into a temporary mode that leads to the creation of healthy new cells. Other research suggests that a very-low-calorie diet may make the body more responsive to cancer treatment and can slow the progression of multiple sclerosis.

A recent two-year study found that people who cut their calorie intake by 25% lost an average of 10% of their body weight, slept better and were even cheerier compared with those who didn't diet.

"Doctors can offer patients this as an alternative to drugs," says Valter Longo, director of the University of Southern California Longevity Institute and founder of L-Nutra. (Longo says he doesn't receive a salary from his work with L-Nutra.)

Still, not everyone agrees that the evidence is strong enough to support the price tag--or the effort required. "I certainly wouldn't do it," says Rozalyn Anderson, a researcher at the University of Wisconsin--Madison, who studies calorie restriction in monkeys. "Life is too short, even if calorie restriction extends it."

The real promise of this kind of research is identifying cell pathways that are involved in aging and activated during fasting, she says. Ultimately this could lead to the development of a drug that could trigger those same pathways without requiring people to eat less.

THE BOTTOM LINE: Occasional calorie restriction does appear to have health benefits, but how much comes from weight loss and how much comes from healthy cell changes needs to be further explored. Widely agreed upon is that any version of a fasting diet should be done under a physician's supervision.

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How Silicon Valley Is Trying to Hack Its Way Into a Longer Life - TIME