Spring Chicken Read online

  You’re not helping, I thought.

  The medical term for male pattern baldness is androgenetic alopecia, and indeed it seems to be hardwired into the genes of many unfortunate men (actually, most men). But in fact, most of Cotsarelis’s patients are women who suffer from basically the same syndrome: Their hair volume shrinks, and the strands get thinner, even if they don’t eventually fall out or “miniaturize” like their husbands’. “It’s interesting,” he observed, “the ones who are most affected by this are the ones who had the most beautiful, dense hair when they were younger. They were in the ninety-ninth percentile.”

  Surprise: Hair loss, or hair weirdness, affects women, too. According to one study, 6 percent of women under age fifty show some degree of actual hair loss—a figure that rises to 38 percent by the time they reach their seventies. For men, of course, it’s much worse: Four out of five will lose major hair by age seventy. But even among those who do keep their hair, nearly everyone will go gray eventually. Why is that? I asked.

  Gray hair is not caused by individual hairs “turning” gray, Cotsarelis explained patiently. Rather, gray hairs are simply hair strands that lack pigment, another symptom of aging follicles. Over time, the pigmented hairs fall out, leaving the gray ones behind. If you’re lucky. Only 5 percent of men or women keep their youthful-looking locks into their seventies, he estimates.

  For the rest of us, Cotsarelis feels our pain: “Evolutionarily, I think the state of your hair was a very important indicator of health,” he said. “If you see somebody with luxurious, thick hair, you know they are not nutritionally deficient, they have to have had enough calories—and they’re probably fertile. But if they’re sick, if they have mange, their hair’s looking terrible, and they’re not attractive. That’s all evolutionarily built in.”

  For most of the Class of 198-, apart from a lucky and annoying few, our barren scalps were telegraphing to the world that we were tired, used-up, and perhaps close to the end of the line—bad bets for swapping genes. Which is why ladies often hesitate to click on bald dudes on Match.com, and why the hair-products industry takes in billions of dollars from both sexes. It isn’t just vanity—it’s evolution. “It’s just an enormous part of our identity and sense of well-being,” Cotsarelis said.

  What had brought me here was the fact that Cotsarelis has done groundbreaking research into how hair follicles can be induced to regrow. In 2012, his team identified a key culprit in hair loss, a molecule called prostaglandin D2 that is often found around the scene of the crime: areas of the scalp that have no hair. The evidence is more than circumstantial: Prostaglandin D2 is known to inhibit hair follicle growth, and is also related to inflammation, which tends to increase in our bodies with age. Merck was testing a drug that inhibited PGD2—inhibiting the inhibitor, if you will—but withdrew it in 2013. Cotsarelis has founded his own start-up company called Follica that is working on its own prostaglandin inhibitor, among other treatments.

  But the real action is with hair stem cells, which Cotsarelis had “basically become obsessed with” during graduate school. Back then, it was thought that we were born with a certain number of hair follicles, and that they died out over time; in fact, Cotsarelis says, follicular stem cells remain intact throughout our lives, but as we get older, they simply go dormant—something that’s true of other kinds of stem cells, too, it turns out. So the question becomes, how to you reawaken the stem cells?

  In 2007, Cotsarelis published a novel paper in Nature that described how he had administered a bunch of tiny jabs to the skin of mice, and waited to see what happened to the skin cells during healing. To his surprise, he found that the wounds triggered a cascade of growth factors that basically returned the skin cells to an embryonic-like state—turning them to stem cells, in effect—and in turn, induced them to generate brand-new hair follicles. Perhaps human scalps could do the same thing, if given the right combination of drugs and jabs. He’s working on that, too, with his start-up.

  So is there hope for my ever-expanding flesh-colored yarmulke? My frontal hairline, in retreat like the Confederate army at Gettysburg? He thinks so, even if he wasn’t terribly forthcoming with the details just yet.

  “But even if we figure out how to treat it, that doesn’t mean we’ll ‘cure’ it,” he cautioned as I left. “I think what we’re doing will end up with treatments, without necessarily understanding it.”

  Curing baldness is pretty far down the list of NIH grant-funding priorities; most scientists who study aging think hair loss is pretty much irrelevant to our actual, biological aging. Evolutionarily, though, the fact that so many of us lose our hair has lots to do with why all of us age. Cotsarelis was right about that.

  Not long after Darwin proposed his theory of evolution, scientists began wondering how aging and death might fit into his framework. Why did we age? How had natural selection permitted aging to exist, since it is pretty much the opposite of “survival of the fittest”?

  In 1891, the great German biologist August Weissmann took a stab at answering that question. He speculated that living things grow old and die in order to make room for the next generation, saving resources so that the young may survive. In his view, aging had been programmed into us for the good of the species, and that the old are meant to die and get out of the way. This theory has been enormously popular with students and everyone else under the age of twenty-five. But the notion that aging is somehow programmed has been hotly debated ever since, and most evolutionary biologists disagree with Weissmann.

  For one thing, scientists have long believed evolution works on the level of the individual, not the group; genes are selected and passed on because they benefit the animal that carries them, enabling him or her to reproduce. The idea of group-based selection goes against that. For another, very few wild animals live long enough to die of old age; most perish much earlier from other causes, such as being eaten. Look at mice, for example. In the laboratory, with regular feeding and a nice cage full of cozy sawdust, a mouse will live about two years before it dies, generally of cancer. In the wild, though, mice rarely live longer than six months, and they generally perish in the mouth of a fox or, far more commonly, from cold.

  So aging is not hugely relevant to the evolution of mice or any other animal, including humans. Our average hunter-gatherer ancestor lived to be somewhere around twenty-five years old, most likely dying from an infection or an accident, or an attack by a predator or fellow human. Only a select few lived into their sixties and seventies—and this, realized the insightful British geneticist and eventual Nobel Prize winner J. B. S. “Jack” Haldane, might actually help explain why we age the way we do.

  Haldane had been studying a condition called Huntington’s disease, which might possibly be the world’s most horrible illness. Basically a very early-onset form of dementia, it starts with subtle changes in personality and balance, but then develops into a torturous, crippling affliction within a few years. Its sufferers almost seem to be dancing as they lose control of their bodies and begin writhing and jerking spasmodically. Perhaps the most famous Huntington’s victim, folksinger Woody Guthrie, spent the last fifteen years of his life in mental institutions before he died at the tragic yet typical age of fifty-five.

  What struck Haldane as odd was that Huntington’s is actually an inherited condition, carried on a single gene. Not only that, but the Huntington’s gene is dominant, meaning that even if only one parent has it, his or her children will have a fifty percent chance of developing the disease. According to the theory of natural selection, such a catastrophic genetic condition should have been bred out of existence long ago. But Huntington’s has one other unique quality: Its symptoms do not appear until around age forty.

  Haldane realized what this meant: Because Huntington’s only manifests itself later in life, after its carriers would have had children, it had remained largely untouched by natural selection. By the time a person realized they had the gene, they would have already passed it on. Thus the Hunti
ngton’s gene was able to survive because it resided in the “selection shadow,” the post-reproductive period of life where the force of natural selection is drastically weakened.

  One of Haldane’s colleagues, the brilliant Peter Medawar—also a future Nobelist—saw the connection to aging. The selection shadow allows all sorts of harmful genes to flourish in later life, not just Huntington’s but many other unpleasant traits that otherwise should have been erased by the purifying force of natural selection: the hardening of our arteries, the softening of our muscles, the wrinkling of our skin, the blossoming of our love handles, and the steady unraveling of our brains. Not to mention the dreaded flesh-colored yarmulke. Once we hit middle age, evolution pretty much takes its hands off the steering wheel and cracks open a beer.

  So whatever purpose me and my college classmates’ luxuriant, youthful manes might have served—plumage to attract mates, insulation for our brains, protection against injury or the sun—they became irrelevant after forty, because evolution no longer cared how good looking we were. Same for our vision, our knees, and our sexual hydraulics. As the geneticist Michael Rose put it, “The latter part of the life cycle [becomes] a genetic ‘garbage can,’ ” which is also where our hair ends up.

  The selection shadow explains a lot of other things, such as why women are much likelier to get breast cancer in their fifties than in their reproductively active twenties. Mothers who were genetically predisposed to early breast cancer would have had a harder time raising babies, and those babies would have been less likely to survive and pass on those early-breast-cancer genes.

  Medawar saw aging as the accumulation of these harmful, unselected-for genes. But what if the very same genes that sculpted us into our magnificent twenty-year-old selves actually end up killing us in the long run? This was the insight of an American geneticist named George Williams, who speculated in a 1957 paper that certain genes that are helpful early in life could themselves have harmful or even dangerous effects later on. This phenomenon was later dubbed antagonistic pleiotropy (pleiotropy referring to a single gene with multiple functions). Moreover, Williams claimed that natural selection would actually favor such genes.

  An interesting example of a pleiotropic gene turned up recently, and it has to do with the fact that white people get tan. Scientists at Oxford University found a gene variant in Caucasians that helps their pale skins resist damage from the sun’s UV rays by temporarily darkening, but at the cost of increased the risk of testicular cancer. To pick another example, scientists puzzled over the high prevalence of the gene for hemochromatosis, a condition that causes dangerously high levels of toxic iron in the blood, leading to damage and disease in midlife. But then evidence emerged from the Middle Ages that men with that gene appeared to have greater resistance to bubonic plague. The hemochromatosis gene gave you better odds of surviving the plague, at the cost of poor health in middle age. To evolution, that’s a no-brainer: The gene stays.

  Aging is full of these kinds of trade-offs, between immediate survival and eventual longevity. The loser, usually, is longevity. In fact, evolution may actually have helped make our lifespans shorter.

  In the early 1990s, a young researcher at UCSF named Cynthia Kenyon discovered a mutation that vastly increased the lifespan of our friend C. elegans, the millimeter-long worm that is so beloved by aging scientists. The mutant worms lacked a gene called daf-2 that governs metabolism—specifically, receptors for insulin-like growth factor, the worm equivalent of our IGF-1. Kenyon found that her daf-2 “knockout” worms lived twice as long as normal or “wild type” worms.

  This was a stunning discovery, the first real evidence that aging could be slowed by deleting a single gene. Not only that, but her discovery showed that the insulin/IGF “pathway” played a central role in aging—and that, contrary to the belief of Dr. Life et al, the less of these growth factors you have, the better. Kenyon asserted that her worms had survived for the equivalent of 120 human years, a claim that made headlines and put her on the long list for the Nobel Prize. No comparable “Grim Reaper gene,” as Kenyon dubbed it, has yet been found in humans, but her discovery gave a tantalizing hint that tinkering with our own genes might extend lifespan.

  Such gene therapy is still years away, and it remains doubtful that anyone could find a single gene with such a dramatic effect on human longevity. (For one thing, C. elegans has only 959 cells, while the human body has trillions.) But the discovery also shed light on the evolution of longevity itself. Common sense would dictate that the long-lived worms should have enjoyed some sort of evolutionarily advantage over their short-lived cousins. So why hadn’t natural selection already eliminated the Grim Reaper gene?

  A few years after Kenyon made her discovery, a Scottish-born scientist named Gordon Lithgow figured out why it had. He mixed normal worms and long-lived daf-2 knockouts in the same dish, to see what would happen. He was stunned by the results: Within just four generations, the long-lived worms were all but extinct. The reason, it turns out, was that the knockouts reproduced ever-so-slightly later than the normal wild-type worms. It didn’t take long before the long-lived mutant worms had been outbred, outnumbered, and overwhelmed by their slutty wild cousins. Their extreme longevity proved to be no help at all.

  Interestingly, this phenomenon has also been observed in long-lived humans; Nir Barzilai’s Ashkenazi Jewish centenarians, for example, tended to have very few to no children, despite having married in the 1920s and 1930s, before the advent of birth control. Or if they did have kids, they did so later in life—another finding that has been associated with longer lifespan. (A side effect of this, of course, has been to make “longevity genes” even rarer.) So perhaps having kids really does shorten your lifespan.

  Lithgow’s worm showdown seemed to prove that natural selection pretty clearly favors fast breeders over the long-lived, for the same reason most towns have twenty McDonald’s for every fancy French restaurant. Cheap and easy generally beats out long and slow. But it also raised other questions, such as: Why do some animals—and some people—live longer than others? Why do humans live eighty years, while mice live only two or three under the best conditions? Why has longevity evolved, at all?

  As it turns out, there are actually two explanations: One has to do with sex, and the other with death.

  Steven Austad hadn’t thought much about aging until the day in 1982 when he met Possum #9. Before that, as his wife observed later, he had been concerned mostly with sex. Possum sex, but still.

  He was camped out in the savanna of central Venezuela, helping a friend trap female possums for a study. Every month or so, they would trap all the local females, evaluate their health, and let them go. One day he recaptured Ms. #9, whom he had first trapped and banded just a few months earlier. Back then, she had been young and feisty, delivering a “solid bite,” he later recalled. Now she was suffering from arthritis and nearly blind from cataracts. When he let her go, she wobbled off and bumped into a tree.

  He saw this sort of thing happen over and over: Within the span of six months or so, healthy young animals “would just fall apart,” he says. “They were aging incredibly quickly.”

  The story got even stranger a few years later, when Austad went to study a different bunch of possums who lived on a remote barrier island called Sapelo Island, off the coast of Georgia. The island possums were basically the same as their Venezuelan cousins, with one major difference: They lived much longer, as much as four years, versus just a year or two for the Venezuelans. The main reason had to do with predators: The jungle possums had lots, but the island possums had none, having been isolated from the mainland for more than five thousand years.

  As a result, they were rather more relaxed. The first one Austad spotted was snoozing in the middle of the road. He ran up and grabbed it with his bare hands. He soon realized that he had arrived in a possum paradise. With no predators, the animals’ lives were virtually stress-free, with nothing else to do but eat, sleep, and breed, which they d
id with gusto. Each Sapelo female produced two or three litters in her lifetime, versus just one per female in Venezuela. It was like a Club Med for possums.

  Austad was not surprised that the island possums lived longer, but what struck him was that they also seemed to be aging more slowly. He examined the tendons in the animals’ tails, and found that the Sapelo possums stayed limber for much longer than the mainland animals, a telltale marker of slower aging; their limbs and joints did not grow old and stiff nearly as quickly. Far from aging at some fixed rate, he realized, the Sapelo Island possums had somehow evolved to age more slowly than their jungle cousins. It was Nature’s version of the class-reunion problem: Some animals get old in the blink of an eye, while others seem to stay youthful forever. But why?

  Unlike most aging researchers, who stay largely confined to their labs, Austad is a bit of a wanderer. He spent the early part of his career as a field biologist in exotic places like Papua New Guinea, as well as Venezuela and the Georgia coast. He’s spent a fair portion of his life sleeping in tents, but it was a lion named Orville who helped instill his keen awareness of his position on the food chain.

  One winter afternoon, Austad drove me to one of his favorite spots, the San Antonio Zoo, not far from downtown. As we strolled around the park, he shared stories and fun facts about monkeys, spiders, pythons, and tree kangaroos, an odd animal that he had studied in Papua New Guinea. Humans nowadays, he observed, age a lot like zoo animals—protected from predators and accidents, we live a lot longer than we ever did in the wild. Eventually we found ourselves outside the lion enclosure, where a young male started giving Austad a hard stare, as if Austad had been hitting on his girlfriend in a bar. Or perhaps he was just bored; it was a chilly day, and the zoo was nearly deserted. Whatever the reason, Austad seemed unnerved, and we moved on quickly.

  “I don’t like to make eye contact with them,” he said. “Even on safari, when we drive through a group of lions, I’ll sit in the middle of the vehicle, not looking out. People think I’m crazy.”