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  “After twenty years of watching it,” he told me, “I was like, Naaah. I got nothin’.”

  Then Wagers suggested they try parabiosis, to see if young blood revived aging hearts. Their preliminary results suggested that it did, so they decided to try to find the factor that might be responsible for that particular effect. Working with a company in Colorado called SomaLogic, they narrowed the search down to thirteen candidates, all of which were growth-related factors of one sort or another. After more analysis, one clear winner emerged: something called growth differentiation factor 11, or GDF11, that was plentiful in young mouse blood, but not in old mouse blood.

  Even better, biotech companies already manufactured GDF11 for research purposes, so they could simply buy it and inject it in their mice, which they did. And lo, it seemed to do the same thing as parabiosis, only without the creepy surgery: Just adding back GDF11 for a few weeks returned the aged, thickened hearts of the old mice to their normal, youthful state. It had set back the clock, they reported in May 2013. This was particularly interesting, because it had been thought that the “young blood” effect mostly worked on stem cells. But heart muscle doesn’t have very active stem cells, so there had to be something else going on. Next, they looked at the effect of GDF11 on aged mouse muscles, and found that it improved their condition, too (good-bye, sarcopenia). More surprisingly, it also seemed to help aged mouse brains, by improving the blood vessels around neural stem cells. The elderly mice had even regained their sense of smell, they found.

  When they first got their results, Wagers’s old friend Lee wrote her a short email: “This could be big.”

  She replied, “I know.”

  They were right: Both studies were published in May 2014, in the same issue of Science, and they made headlines. Along with a third collaborator, Lee Rubin, Wagers and Lee are now pursuing possible drug candidates that would somehow activate GDF11; they have taken out patents, and are working with a venture capital group to fund the research. The goal is to come up with a drug molecule that mimics the activity of GDF11, or stimulates its production in the body. (GDF11 itself is too bulky and difficult to inject every day.) So far, they’re tight-lipped, but the potential is huge: a drug that would treat heart failure, muscle wasting and Alzheimer’s, potentially.

  “This one protein is talking to many different cell types in many different tissues,” says Wagers. “That is fundamentally interesting because it tells you why there might be synchrony in the response of different tissues to age.”

  But she also acknowledges that GDF11 is hardly the end of the story; it’s more like the beginning of a new chapter. Two other major parabiosis-related papers were published the same week as Wagers and Lee’s: In Nature Medicine, Saul Villeda finally reported his results, that blood plasma from young mice seemed to restore youthful sprightliness to old neurons. Across the Bay, in Berkeley, a Russian scientist named Irina Conboy, who had also trained in Tom Rando’s lab, reported an even more intriguing result the very same day (it was a big day for parabiosis): Old muscles seemed to be rejuvenated by dosing with oxytocin, the “trust” hormone that’s associated with sex, love, nurturing, and childbirth—it’s even released when you give somebody a hug. Plus, it’s cheap and easy to get. No transfusion required.

  Not everyone is waiting for FDA approval: I know of at least one private scientist who has tried oxytocin injections on himself, hoping for some sort of rejuvenation effect. (No word yet on whether it’s worked.) And Saul Villeda and his mentor, Tony Wyss-Coray of Stanford, are planning a small clinical trial of their own. Rather than look for the “hay in the haystack,” they plan to simply inject plasma donated from young people into late-stage Alzheimer’s patients, looking for signs of the rejuvenation effect that Villeda had observed in his mice.

  If it succeeds, one can imagine all sorts of scary scenarios, like Donald Trump paying impoverished college students for plasma transfusions, so one almost roots for Wagers’s team to succeed with their parabiosis pill. And there are still many unanswered questions such as whether these “youth factors” might cause cancer.

  In the meantime, I’m just going to go for more hugs.

  Epilogue

  THE DEATH OF DEATH

  Millions long for immortality who don’t know what to do with themselves on a rainy Sunday afternoon.

  —Susan Ertz

  I’ve waited a long time to give you the really bad news about aging, but now I’m afraid I have to inform you that you probably have herpes. Not only that, but there’s an even better chance that your mother does, too (or did). Also your father.

  Don’t feel bad: The herpes I’m talking about isn’t the kind that you get on spring break. Rather, it’s a way in to one of the most overlooked, yet potentially deadly forms of aging: the aging of our immune system.

  Now, about that disease: There are, of course, many different kinds of herpes viruses, such as chickenpox and shingles, in addition to the kissing kind. But there is another, far more common version that is present in at least half of all American adults, yet (normally) causes no symptoms whatsoever. Most people do not even know they have it.

  It’s called cytomegalovirus, which sounds like something out of a science fiction movie, but in fact CMV (as it’s known) is one of the largest and most promiscuous viruses in the human body, with an enormous genome that lets it attack just about any kind of human cell. It is usually fairly benign, hanging out quietly inside us without causing symptoms (it sometimes provokes a mononucleosis-type illness, but that’s fairly rare). But that is not the same thing as being harmless. “There’s some evidence that this virus can do some good things for you when you’re young, like putting the immune system on a higher state of alert,” says Janko Nikolich-Zugich, a leading authority on immune aging at the University of Arizona, “but it takes a toll going further down the line.”

  The problem stems from the way the human immune system normally works—and how it ages. The job of our immune defenses is to defend the body from the invaders, the unwanted, the attackers. With each new infection, we generate T-cells specifically tuned to fight that particular infection, which are sent out like shock troops to battle the latest contagion. All those T-cells emanate from the thymus, a spongy organ that sits more or less in the middle of your chest. If you’ve eaten at a nice French restaurant, thymus was probably on the menu as sweetbreads (or ris de veau). Starting around age twenty, yes you guessed it, your sweetbreads begin to shrivel up and die. It’s one of the first things to go, and it goes almost completely. Which is bizarre, for such a seemingly important organ, but that’s aging for you; the most important stuff is also the most vulnerable.

  Of course, this “involution” of the thymus is irreversible, and eventually the thymus stops responding to new infections (though we do retain pools of T-cells that remember the infections we have already had). So while our youthful immune systems could handle most unfamiliar bugs that we encounter, seemingly minor bugs can kill us when we’re older, if we haven’t seen them before. Case in point: my otherwise robust grandfather, who succumbed to what started out as a pretty basic urinary tract infection. Immune aging is why older people should get flu vaccines; respiratory infections are not really considered a disease of aging, but they kill more people than Alzheimer’s, and they disproportionately affect the elderly.

  The real reason CMV poses a problem, Janko explains, is because it ties up a lot of the immune system’s “bandwidth,” like your teenager playing video games and hogging all the Internet capacity so you can’t stream Antiques Roadshow. “A single bug can occupy half of your immunological system,” he says. People infected with the virus live three to four years shorter, on average. Yet humans have coexisted with CMV for hundreds of thousands of years. “The coevolution of this virus with us is mind boggling,” he says.

  Like a good evolutionary partner, CMV had no intention of killing us, until we started living longer. Over the long run, we now know, the cytomegalomonster begins to weaken us and
make us vulnerable—not only to infection, but also to other aging-related diseases. Like a hostile occupying army, its presence may help ramp up the levels of inflammation found in older adults, which make us susceptible to disease. CMV is particularly strongly associated with preclinical cardiovascular disease, because it targets the endothelial cells in the lining of blood vessels, causing inflammation that leads to arterial plaques—where the virus is frequently found lurking.

  In short, it’s like a guerrilla war, which is something Nikolich-Zugich knows a thing or two about, having grown up in what was once communist-run Yugoslavia. After the fall of the Soviet Union, he watched the country falling apart and realized he would have to make his scientific career elsewhere. He fled to the United States to study at Tufts, and in Boston he lived with a Jewish family that his own father had helped to escape from the Nazis during World War II. He ultimately landed at the University of Arizona, and began studying the immune system. When I met him, he was chairing a discussion on possible ways that we might, one day, be able to eliminate the aging of the immune system, and presumably thus his job, at a stroke.

  The occasion was the sixth biannual SENS meeting in Cambridge, England, a conference put on every two years by Aubrey de Grey, the bearded, beer-drinking self-styled prophet of immortality, since 2003. The gathering was focused on research that might help put de Grey’s complicated anti-aging strategy into practice. SENS, remember, stands for “Strategies for Engineering Negligible Senescence,” and it was born in an epiphany that de Grey experienced, where he realized that the only way to achieve true longevity extension is by altering fundamental human biology, so that we more resemble—on a cellular level—critters like the 500-year-old clam, or the 200-year-old whales, or the thirty-year-old naked mole-rats, who barely aged at all. Merely tinkering with metabolism, which was and still is the dominant research approach, would only get us a few years at best he feels. (Hungry years, too.)

  In its early years, SENS conferences were populated largely by fringey characters, but it has steadily grown more respectable, attracting respected scientists like Nikolich-Zugich. In his session, we heard from not just one but two well-known researchers who were working on competing ways to grow new thymus glands in older bodies. Neither method had really worked too well, so far, but it was a start.

  De Grey himself had evolved since his 60 Minutes heyday; he was no longer just the bearded guy in the pub saying wild things to Morley Safer about living for a thousand years. Nor was he affiliated with Cambridge any longer; the university had dismissed him for creating the impression, advertent or not, that he was on the faculty there. That had liberated him in a way, but even more game-changing was the fact that he now had money to fund actual research. This was thanks to his mother, who had had the prescience to buy two town houses in the Chelsea neighborhood of London in the early 1960s. When she passed away in 2011, they were worth more than $16 million, all of which went to her only son. Aubrey had used some of the money to buy himself a house in the woods in Los Gatos, where he now lives part-time along with one of the two girlfriends he maintains relationships with, while still being married to his wife Adelaide. (“It’s well known that I am polyamorous,” he told me.)

  He plowed the rest of the proceeds into the SENS (Strategies for Engineering Negligible Senescence) Foundation, which meant that he could put his ideas to the test in labs. This itself was a major step: One of the knocks against him was that he had never done the “wet work” of hard bench science. Now he had funding for five years’ worth of experiments. The grow-a-new-thymus project was just one curious project that his mom’s real estate investments had helped to fund and promote. There was also a particularly interesting presentation on how a Mexican cave salamander, called the axolotl, can regrow its severed limbs, right down to the correct number of toes. If only we could tap that kind of regenerative power, then not only would there be no death, but there would be no more Thanksgiving finger-slicings, either. Fun fact: Not surprisingly, cave salamanders are loaded with telomerase. (They are also reportedly now nearly extinct in the wild, alas; so much for longevity.)

  All sciences need the cranks, the fringers, the people who seem nuts; only time will tell if Aubrey de Grey is the one who turns out to be right. Already, there are signs that it’s not completely crazy. For one thing, he had subtly changed some of his emphasis, so that he was not only pursuing the cellular strategies he had first outlined in his manifestos; now, he was embracing all sorts of regenerative biotechnology, some of which is downright attainable. Case in point: the thymus project, which may not be as far-fetched as it seems.

  In April 2014, European scientists succeeded in growing new, functioning thymus glands in old mice by restoring a genetic mechanism that normally shuts down with age. The research was funded by a huge, $9 million EU-funded research initiative called ThymiStem, that was aimed at figuring out ways to regenerate the thymus gland in patients with damaged immune systems. Its founders had cancer patients and chemotherapy survivors in mind, but such a treatment would have an obvious and broader application in older adults. And it had crossed a major hurdle very quickly. So the idea that we might regrow or replace our crapped-out, old organs in some way—during the lifetimes of people who are reading this book—is not completely crazy.

  In the pub at night, the beer and the conversation flowed freely. Few of the attendees seemed to doubt that aging and death would eventually be defeated, and that technology would solve all our other problems as well. To argue otherwise was to risk being labeled a “deathist.” There was even a small protest against the dearth of funding for longevity research, held at a nearby pub (of course).

  We already live in a world where biotechnology can bring back our lost, loved pets, sort of: At dinner one night in the vaulted Queen’s College dining hall, the Silicon Valley finance guy next to me showed me photos of his cloned dog. I was envious. Across from us were two guys in their late twenties. They were roommates, sharing a flat in London as they worked on developing an app, the twenty-first-century version of writing the Great Novel.

  “Why are you guys here?” I asked. “You seem a bit young to be worried about aging.”

  They looked at me like I was nuts. “Because we want to stay like this!” one said finally. “Wouldn’t you?”

  It was hard to argue the point. Who wouldn’t want to stop the clock at, say, thirty?

  But most of the conference presentations, on the other hand, made clear that death is a long way from surrendering anytime soon. Hell, we can’t even grow a decent thymus gland yet—a small, simple organ with only three or four different types of cells. (None of the regenerated thymuses grown to date function particularly well.) How will we keep the whole human body from dying? Until then, I’m doing everything I can to keep myself from falling apart—although I’ll stop short of signing up for cryonic preservation. I’m not sure I want to come back to life in the shape I was in at the exact moment when I died.

  But the truth is that there is no such thing as a “cure” for aging, much less a “secret” (as I had to explain to practically every single one of my friends while working on this book). Aging science has pieced together the edges of the puzzle, but to paraphrase Philip Roth, we still don’t know whether the picture in the frame depicts a battle or a massacre. The secret to aging? Use it or lose it may be the best we can do for now.

  The morning after the conference ended, my head still a bit foggy from the pub, I fought my way onto a mobbed train and grabbed the only remaining seat, which happened to be next to one of my fellow conference attendees and pub buddies, a man named Sundeep Dhillon, who was rather an impressive character himself. In his twenties, he had become the youngest person to complete the Seven Summits, the highest peak on each continent, including Mount Everest. In 1996, the disastrous year chronicled in Jon Krakauer’s Into Thin Air, he had turned back four hundred meters from the summit of Everest, and he had buried a deceased fellow climber on the way down. More recently, he had serv
ed as a combat doctor in the British Army in Iraq and Afghanistan. For fun, he had run the Marathon des Sables, 140 miles across the Sahara. In London, he worked as an ER doctor and also with a health-tech start-up.

  He had spent a fair amount of time on the edge between life and death, in other words. I asked what he thought of the conference, and he immediately brought up the final presentation, which had dealt with the effects of aging research on population growth. SENS had assigned a Colorado demographer named Randall Kuhn to game out various longevity scenarios and their likely effect on world population—a prime objection of those opposed to longevity research. First the good news: If we’re just talking about people living a bit longer, say to 100 or 120 or even 150, then world population won’t grow all that much—which stands to reason, since no matter how healthy they are, hundred-year-olds probably aren’t going to be having more children.

  But the goal of SENS is not just to live a little bit longer, a little bit healthier; the goal is to live a really long time, in perfect, youthful health. Best-case scenario, that means women would not undergo menopause until much, much later—if at all. So a typical female could have four or five children, spread out over a much longer lifetime, instead of the current global average of two-ish. And that bumps the population curve up enormously.

  According to Kuhn, world population is already headed to a likely plateau of ten billion. Delaying aging a little bit, like ten or twenty years, adds another couple of billion. But if SENS’s negligible-senescence strategy is only mildly successful, Kuhn predicted, world population swells to seventeen billion by 2080. And if we add fertility into the equation, and people are able to live twice as long and keep having children, then world population hits one hundred billion by 2170. It was a sobering thought.