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  The idea was not his alone: The notion of “heterochronic” parabiosis, pairing old and young animals, had been suggested several years earlier by Alex Comfort, an early British gerontologist who intuited that there was something very special about youth—how young people resist stress, injury, and disease so much more powerfully than their parents. “If we kept throughout life the same resistance to stress, injury, and disease that we had at the age of ten,” he wrote, “about one-half of us here today might expect to survive in 700 years’ time.”

  That isn’t a typo: 700 years. It’s the stuff of Aubrey de Grey’s dreams. All you’d have to do is stay the same, biologically, as when you were ten. That’s the trick.

  Comfort suspected that there was something in young bodies that gives them their wonderful, youthful powers of resistance and regeneration, and while this thing is extremely potent, it is also ephemeral, seeming to vanish within a decade or so. But Comfort was too busy to do the experiments himself, because at the age of sixty-something he was busy putting the finishing touches on his most popular work, a handy little illustrated instruction manual called The Joy of Sex. So the heavy lifting fell to Ludwig and his lab assistants, who worked for weeks stitching animals together.

  Parabiosis is admittedly a bit creepy; it’s actually banned in some countries. But it sounds a lot worse than it really is. I witnessed a parabiosis surgery on two rats, in a lab at Albert Einstein College of Medicine in the Bronx, and it took about twenty relatively bloodless minutes to cut them open and suture them together. Within a week or so, the incision would heal and their circulatory systems mesh, so that the same blood would be coursing through both bodies. True, more than a third of Ludwig’s pairs died, but survival rates are far better now, and they go on to live relatively contented lives, once they sort out which animal will “lead,” like in ballroom dancing. Certainly, their new, joined existence is more interesting than sitting around in a cage alone all day long. “When you think about it,” one scientist involved in parabiosis experiments half joked, “it’s really pretty boring being a lab mouse.”

  Next, Ludwig and his team did what scientists always do in aging studies: They waited for the animals to die. (Talk about boring.) The results were anything but dull, though. The old rats that had been paired with young animals went on to live an amazingly long time, between four and five months longer than rats joined to partners of similar age. They even survived slightly longer than Ludwig’s sixty-five single control rats, who had not been subjected to the traumatic surgery. Given that lab rats normally live just a little more than two years, this was like extending human lifespan from roughly eighty to nearly a hundred years.

  In other words, Ludwig found that youth is contagious. But why?

  The best explanation he could offer was that the older animals may have been protected from infection, benefiting from access to the younger immune system. The immune system is certainly important to aging, as we’ll see, but was there a more profound reason? Was there something in young blood, some sort of secret youth-giving factor, that helped the older animals live longer?

  It’s an old, old question. As long ago as the thirteenth century, the alchemist-philosopher Roger Bacon asserted that an old man could be rejuvenated if he inhaled the breath of virgins (male, supposedly). Many an old man (and woman) since has sought the company of youth, sexual or otherwise, perhaps with a similar goal in mind. In the sixteenth century, Sir Francis Bacon (no relation to Roger) performed a blood transfusion from a young dog to an old one, who seemed to him quite rejuvenated. And speaking of young blood, let’s not forget the fictional Dracula, who dined on nothing but, and was alleged to be several centuries old—although in real life, the actual fifteenth-century Count Vlad “The Impaler” Dracula only made it to his mid-forties.

  For the time being, even Ludwig could not provide any better explanation of what he had observed, and parabiosis soon fell out of fashion once again. But the questions that it had raised were profound: Something in young blood must carry this power to rejuvenate old animals—but what was it? And why do we lose whatever-it-is with age? What changes inside us, so profoundly that it alters the makeup of our very blood?

  Or should I quit asking these questions and just go get a blood transfusion from my young niece—who, as of this writing, just happens to be exactly ten years old?

  That’s what I needed to find out.

  Chapter 4

  YOURS SINCERELY, WASTING AWAY

  The most mind-blowing thing for me every day is the mirror. I can’t believe what I look like.

  —Neil Young

  I awoke at sunrise to find a strange man sitting by my bed, preparing to strap a rubber mask over my face. Working quickly but gently, he fitted it over my nose and mouth, sending me from a state of groggy half wakefulness into an instant claustrophobic panic. “It’s okay,” he said soothingly. “Just relax.”

  “Mmmph,” I groaned from behind the mask as my arm flopped spastically.

  “Ssshhhh!” he said, capturing my errant arm and pinning it to my side. “Just lie there quietly.”

  I lay back and tried to think about anything but the tight-fitting mask and my very real suffocation phobia. The man in my room was named Edgar, as in Allan Poe, and he was the night nurse at Baltimore’s Harbor Hospital, where I had just spent my third night in a row. I was not here because I was sick, but because I was healthy: I had volunteered for something called the Baltimore Longitudinal Study of Aging, or BLSA, the world’s longest-running study of human aging. Since 1958, government researchers have been monitoring a growing cohort of subjects on their ride down the roller coaster of Time.

  The study was the brainchild of the pioneering gerontologist Nathan Shock, who was one of the first American scientists to study aging at all. After graduate school, he had landed at the Baltimore branch of the National Institutes of Health, where he soon realized that, basically, scientists had no idea how people naturally grow old. For one thing, until the mid-twentieth century there had never been all that many old people around. Also, the gerontologists of the time tended only to study people who were already aged, or even dead.

  Shock’s stroke of genius was the “longitudinal” part: Rather than poke and pick at old people, he would start with healthy folks who were not quite so old, and observe what happened to them as they slowly aged. So instead of comparing a hypothetical average seventy-year-old to a hypothetical average forty-year-old, they would track each individual on his or her unique journey into old age. He rounded up a core group of subjects, mostly fellow scientists and physicians in the Baltimore medical community, and performed all kinds of basic tests and measurements on them. He would then watch as they changed over time.

  Such a long-term project would be almost inconceivable under today’s tight funding deadlines and tenure-track pressures, but Shock’s little study has matured nicely. The BLSA is now following more than thirteen hundred subjects between the ages of twenty and 105. His small office has become the National Institute on Aging. Over the years, NIA scientists running the BLSA have compiled a painfully detailed rap sheet of the crimes committed upon the human body by aging. According to one BLSA study I pulled up on my laptop, average VO2 max—the body’s ability to process oxygen while exercising—declines by 10 percent during one’s forties, 15 percent in the fifties, and 20 percent in the sixties—and, oh yeah, 30 percent in the seventies. One thing that doesn’t decline, however, is subjects’ weight, which packs on relentlessly through the forties, fifties, and sixties. (Thanks, Science.)

  Some of the information has actually helped people. One of the BLSA’s most important findings was that for men, levels of prostate-specific antigen (PSA), a marker for prostate cancer, don’t really matter; what’s important is the rate of change in PSA. That alone has saved thousands of men from needless painful tests and surgeries. More recently, BLSA data has been used to establish the diagnostic criteria for diabetes, and it has also helped researchers understand the patterns o
f progression of cardiovascular disease and Alzheimer’s. But its big question remains largely unanswered: How do you measure aging? Is it possible to determine someone’s biological age, versus their chronological age?

  The BLSA doesn’t take just anybody. I’d had to undergo a thorough screening, with blood tests, a complete physical (minus prostate exam), and many nosy questions about my medical history, all to make sure I was healthy enough for the government to watch me get old and fall apart. If I had any chronic ailments or was taking any medications, including even just ibuprofen, I would have been disqualified. “These,” cracked the intake nurse, “are some of the healthiest people you’ll ever meet.”

  For the privilege of joining this elite cadre, I gladly gave up three perfect August days to serve as a government guinea pig. I would spend every waking moment undergoing tests of one kind or another, and even sleeping on the hospital ward, in a room with a beautiful view of Baltimore Harbor. All told, the government would collect six thousand pieces of data on me, and every few years, I would be required to come back to give them more. Although I would be free to drop out anytime, the study would not necessarily even end when I died: A brochure outlined the option of donating my body to the BLSA. In return, I would be receiving—for free—the best, most complete medical evaluation that taxpayer money could buy. And also, in some ways, the weirdest.

  Already, over the preceding two days, I had been poked, prodded, stabbed, jabbed, drained, and scanned in every imaginable way. It started early on Tuesday, when a nurse systematically relieved me of about thirty vials’ worth of blood. Already queasy from this ordeal—like most men, I do not enjoy watching blood exit my body—I then had to chug a bottle of a sickly-sweet orange-flavored drink, and sit there while she pilfered yet more of my blood, every twenty minutes for two hours, to test how I coped with a massive onslaught of glucose. Or, as they say in Georgia, “breakfast.”

  Some of my blood was analyzed on the spot, but most would be banked in NIA freezers, for use in future research projects. (Note to future civilizations: Please unearth those vials and clone me.) We then moved on to a series of crazy-making cognitive tests that required me to memorize and recite a shopping list that seemed to have been compiled by an insane person, or possibly my girlfriend: “Squid, cilantro, hacksaw, perfume…”

  Everything that could be measured, was. For the first twenty-four hours, I was forbidden to urinate anywhere but into an orange jug, which resided in a cooler in my bathroom. There was more: A prim young woman had taken close-up photos of my tongue, which she had first dyed blue. “This isn’t my favorite part,” she admitted. Mine either. In another room, a friendly, chubby guy had plastered electrodes to my face and tapped me on the forehead with a rubber mallet, twenty times. This was purportedly to evaluate the nerves that stabilize our vision, like our own internal Steadicam. A nurse trimmed my toenails and saved the clippings in a vial so they could analyze my “microbiome,” the community of microbes that dwell inside, on, and around us, and whose importance has only recently been recognized. Further to this end, I learned to my horror, they would also be requiring a sample of my poop. For this, I was given a special collection device that resembled one of those old-time ladies’ hats, like they wear on Downton Abbey.

  I feared only the MRI machine, where I’d be loaded into a narrow, claustrophobic white tube that made horrible screeching noises for more than an hour, as it scanned my brain and then my legs. It wouldn’t be all that different from flying coach to Cleveland, really, but still, I hated the idea. After a little coaxing from the technician, whose name was Bree—“I’ll be right here,” she cooed, touching my arm—I gladly let her strap me to the tray and slide me into the machine, which then recorded images of my brain taking an imaginary vacation with Bree to an all-inclusive tropical resort.

  My stint in the BLSA was, hands down, the highlight of my research for this book. I won’t lie: It was kind of nice to get so much attention for three days, especially for a guy who normally works at home, alone. It was good to be busy. And the tests seemed ridiculously easy (well, except for memorizing that shopping list). It was so much fun that I took to calling it The Blast.

  On my first day, for example, I was marched into a hallway and told to get up and sit down ten times, arms crossed over my chest, while a staff physiologist timed me with a stopwatch, like a football scout. I then had to stand on one foot for 30 seconds, then the other, a test of balance. Nailed it. The physio also timed me as I walked up and down in the hallway with an oxygen mask on my face (they were big on oxygen masks). Aced that one, too. The next day, I had to walk some more—this time, in a state-of-the-art “gait analysis” laboratory, where my movements were recorded by the same kinds of high-speed cameras used by Pixar. I successfully placed one foot in front of the other.

  The vision exam was a breeze, even when they shone headlights in my face, to simulate oncoming traffic, and I got down to the faint squeaky tones on the hearing test. I also put up a pretty good fight against the grip-strength-o-meter, and the leg-extension machine—just like Brown-Séquard.

  But the best part was the way Blast staffers constantly kept telling me how “young” I was, which was true relative to their typical clientele. This alone made it a wonderful experience. The nurses and doctors and physiologists were happy because I only had to be briefed on each test once, and I did everything quickly. I was rocking The Blast.

  Only later did I realize what this meant: that I had only begun to experience real aging. I would come back every three years, and every time, most of the things they were measuring would likely get worse, not better: body-fat percentage, bone density, vision, hearing, strength, cardiovascular health, glucose tolerance (the syrupy drink test, simple but extremely important). Oh, and memory, obviously. Soon I would be forgetting to turn on my cell phone. The interview about my urination habits would become more lengthy and awkward. To continue the liquid metaphors, aging was like a river that flowed in only one direction: downhill.

  All this began to dawn on me about halfway through the quarter-mile walk test, twenty laps up and down the corridor, as fast as I could go. Even though I walked “briskly,” as instructed, I barely broke a sweat. But then it hit me: Someday, this will be hard. Getting out of a chair will become a painful, humiliating ordeal. Just walking a few blocks will seem like a monumental task. And not long after that, I will die. This was actually one of the most important tests, in that regard. Thanks to Blast data, researchers now know that natural walking speed is one of the most accurate predictors of mortality that we have. The slower you walk, statistically speaking, the sooner you are likely to check out.

  I started to get depressed. Yes, I was still in pretty good shape. For now. But aging had barely affected me yet, and frankly, I was being kind of a crybaby about the whole thing. My long, inevitable decline, which is what The Blast would really be measuring, had only just begun. This was as good as it was going to get. Even my height would change—I’d probably never be this tall again, as the study has documented a long, steady decline in stature (due to water loss in the discs between our vertebrae, if you must know). The study wouldn’t end until I died, and not even then if I signed the autopsy consent form.

  That night, I went out and devoured half a dozen Chesapeake blue crabs, among the highest-cholesterol foods there is, washed down with several beers. Because why not?

  A few weeks after I got home, I phoned Dr. Luigi Ferrucci, who then headed The Blast. When he had taken over in 2002, the study had been languishing, as it had since Nathan Shock died in 1989. It was considered unfashionable to study aging in actual human beings, an exercise some molecular biologists derided as “wrinkle counting.” Instead, the National Institute on Aging had spent millions of dollars on mouse studies in a futile search for “biomarkers” of aging, things like cholesterol levels and other blood chemicals that change with age—all to no avail. There was still no really good way to measure aging.

  Ferrucci had been a geriatr
ician, a physician who treated older people, when he was recruited from his native Florence, Italy. In The Blast, Ferrucci saw a huge opportunity: There was no other study like it, no other that would allow him to plot the trajectory of individual subjects as they aged. He modernized the testing procedures and introduced new imaging technology like the MRI and CT scans, as well as broadening the study’s scope.

  In our first conversation, Ferrucci said something I would never forget: “Aging,” he said, “is hiding in our bodies.”

  Aging is hiding in our bodies. What did he mean by that?

  Two things. First, in terms of our biology, aging is a deep, almost subterranean process that begins long before we are even aware that it is happening; researchers believe some aspects of aging actually commence while we are still in the womb. These changes accelerate after we stop growing, at around age twenty, and by the time we realize that we are middle-aged (with or without the help of tombstone-shaped birthday candles) they are well under way. Many studies have shown that poor health at midlife is a direct predictor of both shorter lifespan and shorter healthspan. One study published in JAMA in 1999, based on Blast data, even found that simple handgrip strength in middle age predicted the onset of disability in old age. So Dr. Brown-Séquard had been right about that, too.

  Second, aging is “hiding in our bodies” because we work hard to hide it, much as the previous owners of my hundred-year-old Pennsylvania house concealed its true rotten condition through the clever use of putty, shingles, and paint. According to Ferrucci, evolution has given us various ways to compensate for the effects of aging, “so these changes will have as few consequences as possible.”