A Search for Anti-Aging Secrets Starts With the Blood of 600 Estonians

March 20, 2019 Off By HotelSalesCareers

Silicon Valley runs on two things: obscene amounts of cash and the tales people tell about who they are. Which is perhaps why the Bay Area has rapidly become ground zero for people pursuing one of the oldest mythologies in human history—the legend of everlasting life.

Well, maybe not ever lasting life exactly, but vastly-expanded-and-improved life. Call it healthspan extension, call it geroprotection: Silicon Valley wants to find a way to keep humans healthier for like, way longer. What was once a fringe science is rapidly becoming one of the Valley’s hottest investments, thanks to high profile endeavors like Alphabet’s $1.5 billion bet on Calico and Bezos and Thiel-backed Unity Biotechnology.

Most of the excitement around these ventures rests in the drugs they’re developing—pills to prevent damaged proteins and treatments to flush out toxic cells. But a new company launching today called BioAge, is instead selling a process: a way to predict mortality. And it’s doing so with advanced machine learning, a horde of lab mice, and the blood of 600 especially long-lived Estonians.

See, aging isn’t one disease. It’s the dysfunction of many different organ systems, first little by little, then all at once. It will take more than one molecule to reverse that sput-sput-sputtering out. But immortality research isn’t exactly a high priority for federally-funded research: To date, the National Institute for Aging has tested only 30 compounds, compared to the thousands trialed in cancer research at the NIH. One of those, a drug called rapamycin, has a future in combatting the decline of the immune system. Metformin, a diabetes drug, is currently in trials testing its anti-aging properties. But testing longevity drugs, of course, takes a long time.

So BioAge, based in Berkeley and run by a Stanford bioinformatician, is building a platform that doesn’t require waiting for its subjects to actually age. Instead, it wants to measure biological age using signals floating in a drop of blood. Biomarkers aren’t a new concept; it’s standard practice to use protein signals to guide drug discovery for conditions like cancer and heart disease. But up until now, no one outside academic research has really done it for anti-aging.

There are two good reasons for that: One, anti-aging drugs don’t have a clear path to making money, because the FDA doesn’t treat aging as a disease in its own right. Two, it’s really freaking hard. Whoever figures it out first will have a serious leg up in the fight to plumb the Valley’s fountain of youth.

“These studies take so long to complete; you have to give drugs to a mouse for four years before you get results,” says BioAge CEO Kristen Fortney, who crossed over into the private sector two years ago from Stanford’s Center on Longevity. Her company launched from stealth with a $10.9 million Series A today, with investments from Andreessen Horowitz and AME Cloud Ventures, run by Yahoo founder Jerry Yang. “We’re trying to get that down to just a few months,” says Fortney.

The idea is to find mortality predictors whose signals are just as strong in humans as they are in mice. Studies at Stanford and elsewhere in the past few years have shown that transfusions from young mice can restore liver and brain function in older mice, suggesting that there’s something in the blood that promotes aging, that it can be measured, and that it can be counteracted. (This is where that rumor you heard about Peter Thiel feeding on the blood of young entrepreneurs probably came from. While he’s not a vampire, he is funding start-up where you can pay $8,000 for a transfusion from the sub-25-year-old set.)

Anyway. To find that signal, Fortney’s team needed lots of data. And Estonia, with its socialized health care system and relaxed views about health data privacy, was the perfect place to start. About 10 years ago, the nation’s largest biobank began gathering data on its population at a massive scale: genomics, proteomics, metabolomics, you name it, all combined with medical health records. BioAge picked a cohort of 600 elderly people, and its scientists started to mine their data for longevity secrets.

First, they sorted out the people who died right away or came down with illnesses—cancer, Alzheimer’s, heart disease—from those that went on to live another 10 years or more. Then, using machine learning, they identified molecular differences in their blood, focusing on molecules that humans and mice have in common (so their findings could translate into a mouse-based lab test). At the end, Fortney’s team had found a number of promising proxies for the onset of age-related diseases.

The next step is checking whether those biomarkers will respond to known anti-aging compounds. So they’re about to take a bunch of mice and shoot them full of things like rapamycin and metformin, then see if the biomarkers respond. If all goes well, they can use those compounds to screen against whatever promising chemicals BioAge’s data-mining algorithms turn up—kicking out a thumbs-up, thumbs-down ruling on a new compound in months rather than years.

“Reliable biomarkers would greatly accelerate this whole field,” says Tom Rando, who directs Stanford’s Glenn Center for the Biology of Aging and first discovered the phenomenon of parabiosis—young blood reversing the effects of aging in old mice. He says that while there have been indications that certain molecules might be strong predictors of biological age, there hasn’t been enough data to establish any of them. “If there were good biomarkers out there we’d all be using them,” he says, “but there’s not.”

It’s possible this is all a wild goose chase, and that we already have a powerful biomarker for aging. Steve Cummings, a longtime aging researcher at UCSF, pulled together NIH study data from over 30,000 people over 30 years to look for markers of disease-free survival. The strongest, most consistent signal he found isn’t in blood at all: It’s walking speed. Another good one is how fast you can connect dots of letters and numbers, a measure of cognitive function.

They identified a few molecules as well, like cystatin-C, which tells you how healthy your kidneys are (can’t live without your kidneys), and a few other measurements that reflect inflammation. But even with lots more molecules to work with, Cummings still thinks that blood-based tests are more hype than anything else. “Even 20 to 30 predictors together adds only a little to prediction of survival by age,” Cummings says. “And I’m confident that walking speed alone will outperform any new biological marker.”

That isn’t stopping Fortney, though—or her competitors. Calico is reportedly tracking a thousand mice from birth to death to sift out a few good chemical predictors of morbidity. Given that they launched in 2013, and mice live about four years, the secretive Alphabet offshoot is due for some results. (The company declined to comment on any specifics for this story.) BioAge should be finished with its first round of validation studies before the year is out, and then it can move on to testing novel drugs. Which should give Silicon Valley’s tech titans plenty of new candidates on which to hang their hopes of 100-year-old retirement.

A Search for Anti-Aging Secrets Starts With the Blood of 600 Estonians

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