In 1912, the year he won the Nobel Prize in Physiology or Medicine for his breakthroughs into sutures and vascular surgery, medical biologist Alexis Carrel started a tissue culture of fibroblast cells from the heart of a chicken embryo. He placed the muscle cells in a stoppered flask and had lab assistants replenish the culture medium regularly. The culture proliferated, as he expected it would. Regularly nurtured with fresh poultry extract, the cells stayed alive for another three and a half decades. His findings proved—or so he thought—that cells are naturally immortal. “Death is not necessary,” Carrel wrote, it is “merely a contingent phenomenon.” Soon, he predicted, we would be engineering human tissues from cell clusters and growing replacement organs in vitro. Growing old would be a thing of the past. We, like cells, are meant to live forever.
He was wrong about cells living forever. Fifteen years after Carrel’s death, scientists realized that cells, like us, senesce and then die. But his predictions regarding regenerative medicine may now be getting closer to reality. In recent years, scientists studying tissue engineering managed to print out a fully beating, three-dimensional, two-chamber mouse heart using a modified desktop, ink-jet printer. By filling the ink cartridge with cells, they’ve been able to “publish” functional human kidneys.
This is a time when we can grow human ears on the backs of mice and implant culture-grown lungs into rats. In the near future, specialists say, whenever we need replacement body parts, from blood vessels to bladders, we’ll use rejection-proof artificial organs grown in laboratories using our own cells. “By putting in the parts you need, you’ll be able to extend life by several decades,” explains Anthony Atala, director of the Wake Forest Institute for Regenerative Medicine. “We may even push that up to 120, 130 years.”
Bolstered by such promising discoveries, our understanding of aging is changing rapidly. Outside the field of organ regeneration, other genuine life-extending breakthroughs are being made in model test species. In 2011, Nature reported that dying worms yellow with a pigment called Thioflavin T (or Basic Yellow 1) makes them live 60 to 70 percent longer than the norm. There’s more. Researchers are currently finding clues to longevity everywhere from Texan bat caves (where biochemists are investigating the role of misfolding proteins in long-lived bats) to the soil of Easter Island (where antifungal microbes known as rapamycin can raise the life expectancy of mice by 30 percent or more). Spermidine, a molecular compound found in human semen as well as grapefruit, has also been proven to significantly prolong the life span of worms, fruit flies, and yeast.
These strange-sounding experiments are yielding findings that could affect our lives. Will longevity research yield breakthroughs leading to immortality? Tinkering with the genes in yeast or roundworms has real effects on longevity in those species; that doesn’t mean those genes will perform similarly in humans. And experiments on human cells in vitro do not guarantee similar functioning in vivo. So dying yourself golden yellow will be useless—unless you plan on standing really, really still in an urban center’s touristic thoroughfare. It won’t help you live longer, but sightseers will likely throw consolatory pennies at you.
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There’s no documented validity to any life-extension strategy, but that hasn’t deterred the making, selling, and buying of countless longevity creams, potions, and pills. For $36.95 you get a one-month supply of micronized Longevinex™ capsules, “designed to help Americans live longer.” For $39.95 you get 120 ml. of Clustered Water™, a solution of water organized into clustered structures that ostensibly rejuvenates interstructural cells. For $159 you get 0.7 fluid ounces of Rejuvity’s Ageless Renewal Serum™, containing a specially formulated concentration of Repair-Plex™. Unfortunately, once you start using it, you shouldn’t stop: “If discontinued, then the aging process of the skin simply continues,” explains the website. The fine print on such products can be a great way of pushing more product.
We’ll believe anything—and belief is our most powerful panacea. As scientists conducting clinical drug trials know, placebos are often as potent as medication. If we simply believe we are taking a drug that fixes our problem, our problem can end up fixed—even if we’re just taking a sugar pill. The way belief affects healing is called the expectancy effect. In studies, placebos have proven effective in treating everything from minor headaches and depression to sore joints, irritable bowel syndrome, and skin conditions. Dermatologists can dab inert water onto patients’ warts while explaining that it’s a treatment that eliminates unwanted viral lumps. In 48 percent of such cases, the warts disappear.
Placebos may not cure all illnesses, but inactive substances do alleviate symptoms and offer therapeutic relief in those who believe that they will work. Faith heals. It isn’t sufficient for patients to simply take a placebo without knowing what its effects are: they have to trust that the prescribed remedy will help in order for it to work. If the medical specialist who administers the sham pill explicitly tells patients that it will resolve their complaint, the condition can be cured by a placebo. But if the patient doesn’t believe that the treatment will work, it definitely won’t. (In fact, if we believe the treatment is bad for us, a totally unharmful dummy drug can aggravate a patient’s condition and cause other injurious effects. This is called a nocebo.) Belief, it seems, has the possibility to be as curative as many drugs or treatments.
The placebo effect isn’t fully understood but it appears to be a result of the way beliefs interact with endorphins, the body’s self-made opioids. “The poppy fields of the mind” spring into bloom when the body experiences extended physical activity (as in runner’s high), spicy foods, or intense pain; they are also linked to religiosity. In fMRI scans of test subjects exposed to low-level electric shocks, the pain receptors in their brains light up. When they are given a placebo ointment, however, their brains behave differently. Even though they are being administered the exact same shocks, their pain receptors remain inactive. Instead, the endorphin-manufacturing quadrants of the brain become engaged. “Our brain really is on drugs when we get a placebo” is how the scientists behind these tests explain it. A similar thing occurs to religious believers. When administered shocks while being asked to look at an image of the Virgin Mary, Catholics don’t feel the pain. Their pain receptors shut off, and instead their internal apothecary kicks in.
Belief and placebo are deeply linked, which is why we’re so open to suggestion. All marketers need to do is make consumers trust in them, and their products will have certain positive effects—as long as they aren’t actually harmful. Unfortunately, some antiaging remedies are hazardous to our health. With the rise in availability of modern-day youth elixirs at the beginning of the twenty-first century, the US government formed a Special Committee on Aging to investigate these potions’ supposed benefits. The congressional report’s title summarized their findings: “Anti-Aging” Products Pose Potential for Physical and Economic Harm.
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Unstudied though these products often are, their performance is akin to that of any placebo—it might have an effect. Stem-cell activating and resveratrol-laden age-management nostrums may not help prevent visible signs of aging, but it doesn’t really matter if they work. What matters is that consumers believe they will work. Hopes for creaselessness are bolstered into faith by hypnotic ad copy in fashion magazines: hydroxy acids have exfoliatory antioxidant powers. Kinetin causes humectant agents to remain on the skin longer. Hyaluronic acid’s renewing properties are legion. Copper peptides are where it’s at. You mean you aren’t yet taking the age-decelerating coenzyme Q10?
Marketers often use scientific-sounding jargon, but a 2011 study of wrinkle-reduction creams found that “at best the products had a small effect, and not on everyone.” In other tests, those that sell for inflated prices were outperformed by no-name moisturizers. Double-blind trials show that about 20 percent of participants’ wrinkles can be improved slightly to moderately after six months of serums, while about 12 percent of participants’ wrinkles improve simply when taking placebos.
That hasn’t stopped women from risking delirious sums on the off chance they might shrink a wrinkle. The cost of a 16.5 oz. jar of Crème de la Mer (which bioferments the curative powers of the sea into a light-and-sound-wave-treated elixir users are encouraged to “apply day and night—for a lifetime”) is $1,900. Carita’s “infinitely rare antiaging formula” Diamant de Beauté, containing pulverized diamonds (which obviously makes facial skin last forever), costs $600 for 1.7 ounces. Ads for SK-II, one of the priciest beauty brands in the world, tell of a Japanese monk crafting the cream’s secret formula, a nutrient-rich fluid called Pitera: “After many experiments, he discovered a liquid that seemed to defy aging.”
But even if it “seems” to, that doesn’t mean it “does.” Clinique Youth Surge Night cream claims to suspend age and interrupt time by building on sirtuin technology to “virtually slow the signs of aging.” But sirtuin technology, as I would soon learn, remains uncertain at best.
“Younger-acting skin leads to younger-looking skin,” claim ads for Olay Professional Pro-X Age Repair Lotion, which signals the moisture barrier to perform “more like it did when it was younger.” Pro-X research is based on “one of the great scientific achievements,” explains Olay’s website: the sequencing of the human genome. Its efficacy is “proven,” explain advertisements. But according to some consumer testers, using it on half of one’s face while using a vastly cheaper cream on the other leads to no noticeable difference. Other testers, though, report favorable results.
Beyond their logic-stretching promotional slogans, nothing much supports the claims made by most antiwrinkle eye-cream manufacturers. Some evidence suggests that compounds called retinoids may have an effect on photo-aged skin, which has suffered prolonged exposure to UV radiation. A study funded by UK chemist Boots found that their own No7 Protect & Perfect Intense Beauty Serum benefits users with sun-damaged skin who apply it for at least a year. (Since the study was made public, sales have skyrocketed: a bottle of the product is bought every eight seconds at Target.) Regardless of efficacy, we spend billions on cosmetic wrinkle-reduction treatments every year. Even young people are getting in on it: in 2011, Walmart announced a new line of cosmetics with antiaging properties aimed at eight- to twelve-year-olds.
While cosmetic skin creams can contain heavy metals and other toxins, they aren’t as dangerous as the use of human growth hormone (HGH), whose use as an antiaging remedy or for age-related problems is not authorized by the FDA. Covertly used by pro athletes and bodybuilders, there’s a false perception that HGH can make people younger. On the contrary: the misuse of growth hormone has been shown to cause organ malfunctions and tumor formation in test species, as well as an “increased probability of early death,” the most perfectly ironic side effect to a remedy hyped as having life-extending qualities. (Things haven’t changed much since the time of the Han dynasty.)
We don’t know exactly how hormones affect us. Preliminary results of a six-year, $45 million National Institutes of Health study of testosterone therapy among elderly men will be available in 2015. In the meantime, HGH and other supposedly age-defying hormones remain procurable online, as do books such as Grow Young with HGH: The Amazing Medically Proven Plan to Reverse Aging, by Dr. Ronald Klatz, MD, DO, “a world recognized authority on preventive medicine and advanced biotechnologies.” Klatz is the president of the American Academy of Anti-Aging Medicine (A4M), an organization whose position statement is that “Aging is no longer inevitable.”
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We’ve tried to explain the causes of growing old in many ways. One of the twentieth century’s most discussed theories of aging is the oxidative model. In the post-World War II years, a chemist and biogerontologist named Denham Harman suggested that aging is caused by cellular exposure to oxygen. This basic concept has obvious appeal based on a causal truth: air makes things age. Just as it causes a cut apple to brown or uncorked wine to oxidize, it weakens our mitochondria. Hence the notion that if we could only prevent oxygen from invading our molecular structure, we could prevent aging.
Antioxidants—the phytonutrients found in colorful fruits and vegetables—seem to protect the body from free radicals, the intercellular equivalent of terrorists. But nobody knows for sure. Numerous other experiments have given rise to doubts that oxidative damage is the main cause of aging. Antioxidant-based vitamin supplements may not limit bodily oxidative damage or even influence aging whatsoever. We can’t say. The answer is blowing in the mitochondrial wind. But the dearth of evidence hasn’t prevented this idea from being accepted as a proven fact, especially among canny marketers.
“In simple language, we don’t get old, we rust from oxygen,” announced Dr. Harry B. Demopoulos in 1989. An occasional actor with a baroque comb-over, Demopoulos was among the first to theorize that consuming antioxidants might slow aging. His company, Health Maintenance, Inc., supplied Hollywood celebrities with a patented blend of vitamins, generating an estimated $10 million in 1990. Since then, sales of antioxidant superfruits such as açaí and blueberries have soared.
In 2002, UC Berkeley’s Dr. Bruce Ames, a winner of the US National Medal of Science, launched a product called Juvenon whose antioxidant supplements have the tagline “Stay Young.” Another company, Eukarion, joined the fray, licensing its discoveries to Estée Lauder. The excitement over Eukarion slowed when the mania for free radicals started fading.
Today antioxidant superfoods are available at most supermarkets, in a multitude of forms. Consuming them won’t make us live longer, although they may make us healthier. “Antioxidants haven’t extended life—that whole idea is out the window,” one senior researcher at the US Department of Health & Human Services’ National Institute on Aging told me. “Things we thought we understood we realized we don’t. The simple ideas just don’t work. There is so much we don’t know.”
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Cynthia Kenyon is a molecular biologist at UC San Francisco whose findings appear to contradict what we assume we know about aging. Her genetic work on roundworms called C. elegans has demonstrated that they can be made to live four times longer than normal. “That’s not immortal,” she concedes. “That’s not to say that you couldn’t. But we haven’t.” She feels confident that her discoveries will translate into human applications. On her website, she has posted a special section for nonscientists in which she explains her views: “We don’t know yet, but to me it seems possible that a fountain of youth, made of molecules and not simply dreams, will someday be a reality.”
Her position is precisely the opposite of another UCSF scientist, Leonard Hayflick, an evolutionary biologist and anatomist who has spent his career working with cells and debunking false scientific claims about immortality. He’s best known for positing the Hayflick limit—that somatic cells can only divide a certain number of times, after which they senesce and die. (Previous to his demonstration of this phenomenon, cell populations were thought to be immortal.) The biological cause of aging, Hayflick says, “is the same as the cause of nonbiological aging—it’s the second law of thermodynamics.” Everything, he asserts, eventually breaks down, collapses, and falls apart. That’s the nature of entropy; and entropy is a fact of nature. “Let’s take something infinitely simpler than your body and mine: automobiles,” says Hayflick. “Even if you put the car in a garage and don’t use it, it won’t stand there forever. Eventually, it will age and disintegrate. This is an inevitable law of physics.”
Kenyon, on the other hand, starts speeches by rejecting such reasoning as old-fashioned. “In the past,” she states, “we thought you wear out, like an old car.” Her colleague the MIT molecular biologist Lenny Guarente, who studied stress in yeast and found that certain genes express themselves in those that live longest, puts it this way: “The wear-and-tear theory is best viewed as a laudable initial attempt to come to grips with the problem, but is not a serious scientific theory; the problem is that people turn out to be more complex than Chevys.”
The difference between inanimate objects and biological organisms, the two point out, is that living systems have self-repairing mechanisms. True, Hayflick and his peers concede, but our body can repair itself only for so long. “Aging occurs because the complex biological molecules of which we are all composed become dysfunctional over time as the energy necessary to keep them structurally sound diminishes,” explains Hayflick. As we age, the defense and maintenance programs that protect us when young gradually stop working.
What if we could find a way of activating such genetic pathways later in life? Scientists have done so with worms, yeast, fruit flies, and mice. The names for these longevity genes are usually technical: SIR2, InR, p66Shc, fos, chico, age-I. (One exception is the recently discovered fruit-fly gene INDY, which stands for “I’m Not Dead Yet.”) The results are indisputable, but interpreting them is another issue altogether. “When single genes are changed, animals that should be old stay young,” Guarente and Kenyon summarized in a Nature article about genetic perturbations that increase life span in simple animals. “On this basis we begin to think of aging as a disease that can be cured, or at least postponed.” Of course, not everyone agrees with their conclusion. It’s certainly a leap to go from genuine genetic findings to speculation that aging in humans is a curable disease.
If anything certain can be gleaned from the current public argument between evolutionary and experimental biologists, it’s how limited the scientific understanding of our aging actually is. The deepest researchers in the world today still don’t know whether there’s a universal biological process behind aging. One side, composed mainly of experimental genetic biologists with ties to pharmaceutical companies, believes that we will be able to manipulate longevity genes in all species. They hope to translate the findings they’ve made on a molecular level into human-ready medicines. On the other side, evolutionary biologists don’t think we’ll ever have the ability to intervene in fundamental human aging. For the rest of us, seeing aging as a disease or not is a personal choice.
Ending aging is for now as elusive as ending time, but scientists have found aging research to be fantastically rewarding financially. In 2008, GlaxoSmithKline paid $720 million for the rights to exploit pharmaceutical drugs based on the genetic pathways uncovered by Guarente and his graduate students. “What we’re working toward is a drug that gives the benefit of exercise and diet without having to exercise and diet,” explained Sirtris’s cofounder David Sinclair, in a statement that neatly encapsulates the contemporary American dream.
Their findings remain inconclusive, at least in human medicine. GSK executives defended their expenditure as high risk—a shot in the dark with the possibility of a high return. Their inferences may prove to be useful, but an inference is not something meant to be believed; it’s meant to be tested. Once the testing is further along, we’ll know more about whether aging genes can be affected in humans.
“I doubt that aging can be reversed,” says Hayflick. “Aging is a random, stochastic process that occurs after reproductive maturation and results from the loss of molecular fidelity.” Guarente, Kenyon, and fellow experimental researchers contend that the genes they’ve isolated have the power to keep an animal’s “natural defense and repair activities going strong regardless of age.” As they wrote in Scientific American, these genes, in lab species, can “dramatically enhance the organism’s health and extend its life span. In essence, they represent the opposite of aging genes—longevity genes.” Heady, but such hopes always have been.
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In both biology and reality, the end begins at the cellular level. Without exception, flora and fauna consist of cells. Our bodies are made up of trillions of cells doing what cells do best, which is making replicas of themselves. Then they die.
For most of history, life consisted of unicellular organisms popping around. To this day, the majority of creatures on earth are single-celled. When a single-celled organism such as a bacterium or a protozoan reproduces through binary fission, what was one becomes two. In some cases, such as division in a yeast or E. coli, clearly a younger cell and an older cell result from each fission. The young one gets all new parts, and the older one gradually senesces. And on it goes.
In other cases, there appears to be no distinction between the progeny and the original cell. The two fission products are effectively clones. There are two ways of describing what happens here: the parent cell either dies while becoming two identical offspring, or it gives birth to an identical replica of itself that will also divide again at the same moment as the parent. Whether the initial cell dies into twins or gives birth to itself, both definitions are valid, and they both showcase the limits of language to explain natural processes.
When cells started getting specialized in order to aggregate into more complex organisms, they became two distinct types of cells: germinal cells and somatic cells. Our soma cells constitute the majority of our body. Our germ cells are those in our gametes—the female ova and the male spermatozoa. Somatic cells age and can replicate a finite number of times (known as the Hayflick limit). Germinal, or reproductive, cells, however, have the capacity to keep on dividing more or less continually. They contain the hereditary information in DNA that is passed on through subsequent generations.
A benefit of ovigerous sexual reproduction is greater complexity for the entire species. Each descendant obtains a bit of both parents’ germ cells. This form of ever-radiating genetic diversity is a defense against potential threats. Even if a large swath of the species gets wiped out by a genetic invasion, some part of the population is likely to be immune. But when species do go extinct, their genetic code disappears. Species are not immortal; nor can what’s lost be re-created.
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The mysteries of the cell may one day reveal something about aging that we don’t as yet understand. For example, just as certain single-celled organisms are capable of regenerating themselves seemingly endlessly, so can cancerous cells. The replicative capacity of a normal cell is finite; cancer cells are simply normal cells that mutate and, for some reason, begin to proliferate continually. The cell buildup is what’s called a tumor. Within each of us, stem cells also have the ability to make apparently limitless copies of themselves, but they are usually quiescent, active only in youth or in a medical emergency.
Cancer cells, stem cells, and unicellular organisms that experience unstoppable growth are spoken of as having cellular immortality. This does not mean they are indestructible. They are not undying. When a host body dies of cancer, the uncontrollable cancer cells die with it. So-called immortal cells can keep dividing in the correct medium (as with the cells of Henrietta Lacks, known as HeLa cells), but obviously they perish if taken out of that culture. Cellular immortality doesn’t mean we can orchestrate the immortalization of life-forms.
In the nineteenth century, August Weismann, author of "Upon the Eternal Duration of Life," wrote of how immense numbers of organisms “do not die.” Our somatic cells perish, he conceded, but germ cells are “potentially immortal” as they can transfer themselves into a new individual. Even though we die, if we have children, our genetic information outlives us.
Just as cells make copies of themselves, our bodies evolved to live long enough to reproduce. We reach our peak in our twenties and start going downhill in our thirties and forties. In our postreproductive period, many of the exact same genetic processes that contributed important and valuable functions in our youth start to have harmful effects. This phenomenon, technically known as antagonistic pleiotropy, is one of the biggest obstacles to solving the aging riddle. Genes involved in cancer or Alzheimer’s are also those that promote healthy growth earlier on. Aging-related illnesses are the price we pay for living to eighty.
Immortalists make much of how certain jellyfish, sponges, corals, and deep-sea creatures appear not to senesce. That these creatures lack nervous systems or memory isn’t an issue. They “don’t age,” prolongevists say. They “may be practically immortal.” Yet as slowly or imperceptibly as they age, they die when killed. Some of them can sprout new limblets if the conditions are favorable or bud body parts, but that doesn’t mean they are eternal.
The freshwater hydra is a tiny, brainless organism with fascinating regenerative capabilities. Even if much of it is killed, it can spring back to health, giving the impression of imperishability. Imagine a three-millimeter-long tube topped with dreadlocks. The hydra is often compared to a fountain, its body a jet of water that shoots into a splash of tentacles. The tube is made up of cells that seem to be both germinal and somatic. As the tube’s old cells age, die, and are sloughed off, new ones are generated. Being hermaphroditic, a hydra can bud off some of those cells into entirely new hydra. It can also rebuild itself from almost any bit of its body. Still, as amazing as it is, it isn’t immortal. It’s a simple organism whose body cells are also germinal cells. Take it out of water and it perishes.
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Whether or not we consider immortality a feasible aim, specialists have made insights into the lengthening of lives—although there’s nothing simple about their discoveries. One of the earliest scientifically replicable means of delaying aging is known as caloric restriction (CR). Eighty years ago, scientists realized that limiting the diets of lab rodents increased their longevity by 40 percent.
Feeding model organisms just enough calories to fulfill their minimum nutritional needs does appear to extend lives in everything from fish to apes. Protozoans that normally live for a maximum of thirteen days can live for up to twenty-five days on CR. In rhesus monkeys studied for twenty years, CR also delays the onset of age-related diseases. Not surprisingly, this has led to rampant speculation that CR might work higher up the phylogenetic ladder as well.
We’ve suspected as much for centuries. The pioneering proto-gerontological researcher Luigi Cornaro (1467–1566) was a Venetian nobleman who lived to his late nineties by eating only twelve ounces of food a day. He outlined his precise regimen in Discorsi della Vita Sobria. He spoke of being healthy, satisfied, and full of joy at a time when most were “sad, sick, and bored.” But modern research into CR suggests that the diet isn’t all smiles and satisfactions.
CR is currently being studied in humans under a multiyear program called CALERIE (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy), funded by the National Institute on Aging. As of 2013, CR hasn’t been proven effective in humans, but even if it were, there are numerous catches.
To begin with, few people want to be hungry all the time in order to live longer. That doesn’t mean there aren’t practitioners out there. They’ve been dubbed the Skinnies by the media, and they eat just enough to stay alive. To follow the regimen requires establishing your daily caloric usage; then you need to eat around 20 to 30 percent less. The diet allows approximately 1,500 to 1,700 calories a day for women, and 1,800 to 2,000 for men. If overseen by a certified nutritionist, the program is not malnutrition—in fact, eating tomato soup with celery sticks for dinner is optimally healthy. It’s just hard to do. And there are—as there always are—side effects. Not only do you lose weight, you end up looking gaunt and sallow. Those in CALERIE complain of often feeling cold—the same phenomenon occurs with underfed rodents, who shiver away hungrily in their cages. Caloric austerity also carries a heightened risk of bone-mineral deficiencies, lowered blood pressure, and anemia. If undertaken without medical supervision, it can also lead to anorexia—and one out of five anorexics ends up dying of complications from the disease. Perhaps the greatest deterrent is the resultant infertility: mice on CR completely lose their sex drive. Their human counterparts can also experience a plummeting libido.
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Sexual malfunction has a murky relationship with longevity. Certain mutant strains of yeast that live 50 percent longer than average also forsake the ability to reproduce. The same mutation that causes their sterility also causes longevity, explains Leonard Guarente, whose team first noticed the coincidence. There is more evidence of this link. Decades-old studies from mental institutions demonstrate that castrated men live an average of fourteen years longer than noncastrati. Worms who’ve had their gonads excised also experience extraordinary longevity.
Cynthia Kenyon, who has used laser beams to zap the sexual organs of roundworms, found that hormones produced by their reproductive systems appear to have an effect on aging. A single mutation in a gene called age-I, linked to fertility, can extend life spans in worms. No one knows what might happen if these results were transposed onto sentient beings. Kenyon has focused on a suite of genes known as DAFs, and she argues that there may be a way of kick-starting their human equivalents, creating her hoped-for fountain of youth made of molecules rather than dreams. In other words, she believes that we will soon find a pill that activates age-influencing genes without having to practice caloric restriction or to castrate ourselves.
The goal of finding a pharmaceutical means of reproducing the health benefits of CR has long tantalized scientists. In 2002, one promising CR mimetic called 2DG made a splash until it was found to have a major flaw: in only slightly higher than recommended dosages, it is toxic and can lead to cardiac mishaps. A company called BioMarker Pharmaceuticals, Inc., has been exploring the CR-like effects of an antidiabetic medication called metformin, which may have potential but has also been shown to cause death from lactic acidosis. By far the greatest source of optimism is sirtuins, the family of genes discovered in yeast by Guarente and his team. If GlaxoSmithKline’s billion-dollar investments prove correct, we may soon be able to take a capsule that triggers sirtuin pathways, allowing us to eat whatever we like, as David Sinclair suggests, while still receiving the biochemical effects of CR.
Some scientists studying other facets of CR express doubts that there will ever be any pharmacological means of triggering the complex interaction of the various genes involved in longevity. “My perception right now is the effects of calorie restriction are multiple,” says Dr. Luigi Fontana of the Washington University School of Medicine’s Center for Human Nutrition, “so I think it’s highly difficult to find one or two or three drugs that will mimic such a complex effect.” It remains to be seen whether a pill or pills will be made available for human usage. Even if a cocktail of age-defying drugs were released, nothing suggests it would be riskproof.
For now, sirtuins and CR appear to have something to do with aging, but that doesn’t mean they are the aging process itself. “Sirtuins are a sexy narrative, that’s for sure,” one source close to the research, who asked not to be named, told me. “Imagine: an antique, archaic gene that came bubbling out of primordial sludge—it’s beautiful.” Almost as beautiful as another sexy narrative that captured the media’s interest in the 1990s.
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Telomeres are snippets of DNA at the ends of chromosomes. The lay description of a telomere is that it’s the cellular equivalent of that plastic tip or cap on the end of a shoelace. Telomeres are devices that prevent genetic data from fraying. As a cell divides repeatedly, its telomeres eventually grind down. The wearing out of a telomere brings with it the death of a cell.
Imagine there was a way of preventing telomeres from shortening. In the 1990s, the same scientists who discovered telomeres also discovered an enzyme named telomerase, which, when added to cells in culture, allowed telomeres to maintain their structural integrity. As the telomeres stay long, cells can divide endlessly. The life span of such telomerase-enhanced cells can be prolonged indefinitely. This was an amazing discovery; but just because cells in vitro can be manipulated does not mean that telomerase can make humans live forever.
It’s a fundamental difference, but one the media had trouble understanding or explaining. Journalists declared that scientists had finally found the microchemical fountain of youth in the form of an “immortalizing enzyme.” It was widely reported that the length of one’s telomeres directly determined one’s life span. Aging would soon be a thing of the past.
Alas, the idea that telomeres are the sole cause of senescence is a simple misapprehension. Just because they play a role in cell aging doesn’t mean they are the mechanism of aging. Telomerase does not eliminate the disease of aging—but it does play a role in the uncontrollable proliferation of cells afflicted with cancer.
The scientists who made the discovery, Elizabeth H. Blackburn, Carol W. Greider, and Jack W. Szostak (who together won the Nobel Prize in Physiology or Medicine in 2009), are still trying to understand the role of telomeres in aging, as well as the effects of telomerase. “Everybody wants to find that there’s a great simplifying principle,” explains Blackburn—but telomeres and aging are anything but simple. To counter all the hype, her colleague Greider wrote a paper explaining that telomere length “is clearly not directly correlated” with longevity. Telomere research has the potential to offer insights into how we age, and into fighting cancer, but for now what it really reveals is the mechanism whereby chromosomes deteriorate as cells divide.
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Whether or not the elimination of aging and death are possible end points, many researchers have formed companies that court or are funded by the multinational pharmaceutical industry. While the idea of Harvard and MIT biologists in bed with giant corporations may seem upsetting to nonacademics, it’s been a growing reality in the field for the past two decades. “In the early 1980s, it was nearly unthinkable for academic scientists to found for-profit corporations,” explains George Washington University professor of law Lewis D. Solomon. But by the 2000s, the situation had changed completely. As Nobel laureate Eric Kandel stated in 2003, “These days, it’s hard to think of a really good biologist who isn’t involved with a company.” Guarente portrays the division this way: “My lab tries to learn more and more about the basic biology underlying aging and survival. The company, meanwhile, is trying to translate this knowledge into drug development.”
Adding to the complications of academics-cum-businessmen, scientists at major institutions occasionally make unverifiable, potentially irresponsible statements to garner publicity and grant funding. Attracting investments from the phalanx of wealthy older Americans looking to sink their private fortunes into the war on aging takes snazzy sales pitches, not dry displays of data collection. Professors with connections to Big Pharma may honestly desire to help civilization, but the skewed gold-rush aspect of longevity research means even the most scrupulous academic biologists stand to benefit personally from misunderstood discoveries. Because the potential for personal gain taints most aspects of aging science, trustworthiness can be hard to gauge.
This is nothing new. In the nineteenth century, John Stuart Mill said that there is no scientific evidence against the immortality of the soul except for negative evidence, meaning the absence of evidence that it exists. In earlier times, promises of immortality were a way for the powerful to maintain power over other people. By hanging the threat of eternal damnation over their heads, the ruling classes could keep civilians in line. For this reason, Mill’s predecessor Hume considered the notion of an afterlife to be a barbarous deceit. “There arise, indeed, in some minds, some unaccountable terrors with regard to futurity,” Hume wrote, “but these would quickly vanish, were they not artificially fostered by precept and education. And those, who foster them: what is their motive? Only to gain a livelihood, and to acquire power and riches in this world. Their very zeal and industry, therefore, are an argument against them.” Exploiting the fear of death is a venerable, often lucrative, tradition.
Longevity studies still occupy a windswept limbo-land where the distinction between pseudoscience and verifiable research is often intentionally obfuscated. A measured approach is usually an indicator of reliability in a researcher, but many well-regarded aging scientists demonstrate a lack of reticence when making sweeping declarations about ending the disease of growing old. Take this twenty-five-year-old example: “We absolutely have within our hands the technology to manipulate and reverse ageing in every tissue and system.” The intervening decades would seem to refute that claim, but it hasn’t stopped such proclamations. In a 2011 open letter, biotech company Sierra Sciences wrote of an urgent need for investors when they lost funding during the recession: “It is no exaggeration to say that we are on the brink of actually curing the disease we call aging!” Actually, most rational humans would agree that statement is an exaggeration. However, Sierra Sciences was unarguably on the brink of something else: bankruptcy. The letter, circulated widely on antiaging websites, appealed for $200,000 a month to keep the lab operational; if no one stepped up, they wrote, it “would be a tragedy for humanity, as well as a missed opportunity to create a multi-billion dollar industry.”
To understand how scientists appear to get ahead of the themselves in seeking investors, it’s worth glancing at the saga of a corporation called Geron, whose stock soared when the telomerase story broke, in much the same way Sirtris’s did when sirtuins had their moment in the spotlight. One of the company’s founders, Michael D. West, was exceedingly vocal about his optimism that telomeres are the solution to human aging. In March 1990, West sent a breathless newsletter to investors about “the spectacular events unfolding. . . . We can take senescent (old) cells and make them immortal. . . . We have found the genes that regulate aging.”
Within ten years, he wrote, the technology would be engineered into a form that could be administered to people. Ten years later, no longer with Geron, West boasted to media that he was “close to transferring the immortal characteristics of germ cells to our bodies and essentially eliminating aging.” Ten years after that, more interested in stem cells than telomeres, he gave a lecture, “The Practical Uses of Immortality,” in which his predictions hadn’t really changed: “The potential applications in age-related degenerative diseases are the demographic trend of our time. It’s going to be the story of the decade. So I think whenever you see opportunity like that, it’s imperative to seriously consider it from a business standpoint.”
But those who consider business opportunities for a living caution against taking him too seriously. A feature in BusinessWeek magazine questioned West’s credibility: “Mention West’s name to fellow scientists and they either sigh, cringe, or ask, ‘What has he done now?’” As Carol Greider, one of the Nobel winners for telomere research, put it, “I never saw any science that he did that was that interesting. He was always just promoting ideas.” The head of Sierra Sciences, however, considers West a guru.
A spectrum of people are engaged in cutting-edge antiaging science, from salaried researchers to self-professed bio-authorities to autodidact hobbyists to passionate longevists eager to sample any life-prolonging drugs. The greatest hype-man of this era, however, is indubitably Aubrey de Grey. His book "Ending Aging" notes that aging kills one hundred thousand people a day—“many old people, yes, but old people are people too.”
An amateur gerontologist, de Grey gained mainstream credibility everywhere from "60 Minutes" to TED Talks, often leaving the impression that he was a biology “professor,” when in actuality he only had a part-time job as a computer programmer for the University of Cambridge. Nevertheless, he has been depicted in conference bios and in the media as a “professor at Cambridge’s Department of Genetics.” It’s the sort of blurred logic that typifies much of his work—the semblance of factuality trumps actual factuality.
De Grey’s former supervisor, Michael Ashburner, a genuine professor of biology at the University of Cambridge, reports that he reprimanded him several times for misrepresenting his position. When I contacted Ashburner to sort out the truth, he explained that de Grey was never a professor employed by the university. He also called de Grey’s gerontological activities “nonsense.”
One of de Grey’s contributions to the field of aging research is a concept he calls WILT: Whole-body Interdiction of Lengthening of Telomeres. WILT is his way of curing cancer. The idea came to him in an Italian café: if we could only excise the gene that produces telomerase from the human body, then we could eliminate cancer. Telomerase, which is active in cancerous cell growth, isn’t usually turned on in normal cells. WILT would do away with it entirely. The problem is that, even if we could do away with the gene behind telomerase, it is vital in the creation of new blood cells.
De Grey’s solution? We’ll just inject ourselves with genetically engineered stem cells whenever we need to.
* * *
The trope of scientists striving to attain immortality, which makes them deranged and evil, is such a cliché it occupies its own subgenre in science-fiction fantasies, from Frankenstein to the Highlander movies. The gamut of unsavory immortals includes vampires, ghosts, zombies, werewolves, aliens, and witches. Infinite tales describe the downside of unendingness, the boredom, disinterest, and despair of being unable to die.
In "Gulliver’s Travels," Swift tells of the Struldbruggs, immortals whom Gulliver assumes must be the happiest people ever. But, it turns out the immortals hate being condemned to perpetual continuance. They are peevish, friendless, morose, and have terrible memories. Because language evolves, they speak weird, old dialects nobody understands anymore, and therefore they barely ever talk. When they do, it’s to spout envy toward people who can die. They’re bitter, crotchety grumps whose message for the rest of us is that living forever might be the harshest curse imaginable. We only imagine immortality being a good thing, Swift concludes, because of the imbecility of human nature.
But immortalists today would say that Swift committed a newbie mistake called the Tithonus error—the presumption that extending life would also extend those difficult years at the tail end of most elderly lives. (When the goddess Aurora beseeched Zeus to immortalize her lover, Tithonus, she neglected to request eternal youth as well; decrepitude ensued.) On the contrary, contemporary longevists explain, defeating aging will mean eliminating that entire period. As de Grey sees it, “There will, quite simply, cease to be a portion of the population that is frail and infirm as a result of their age.”
The only simple truth in the aging world is that nobody understands exactly how aging works. Exhilarating theories abound claiming to explain it. Whenever a good story combines with a whiff of scientific respectability, pills are readied to capitalize on the hype. But what would happen if we could really live forever?
* * *
To find out, I decided to meet with modern-day eternalists, to attend their gatherings, to spend time with them and discuss their worldview. Looking for an insider connection, I tried to interview the Japanese architect Arakawa. He lived in Manhattan and designed homes that could “counteract the usual human destiny of having to die.” Unfortunately, it turned out that he’d died a few months earlier. Then I set about tracking down the astrologer Linda Goodman, whose step-by-step guide to never dying includes visualizing your cells spiraling in reverse. She, too, had passed on. I phoned Dr. Daniel Rudman, who’d told the New England Journal of Medicine in 1990 that “growing old is not inevitable.” But the inevitable had taken him, too.
I considered paying a visit to People Unlimited, a group of “physical immortals” in Arizona focused on living now and forever. Their motto is “It’s time to end death and it takes a community of like-minded individuals to do it.” They are united in their belief that every human deserves deathlessness. “Why do we need to die? It makes no sense,” writes one recruit, Caleb Escobar, in the site’s comments section. He then adds, “I’m not living to die, I’m living for a major reason—TO LIVE!” Followers speak of how they experience “zero struggle” and feel totally freed of all limits. Dean Moriki’s testimonial explains that he joined PU after his wife suffered a stroke and became disabled: “It was a major change from a normal life to a daily living with a wheelchair involved. We divorced soon after.” Since then, he’d become convinced of his noncorruptibility and now lived without suffering or disease. Poof! Magic. The denial was so astounding—and also disconcerting—that I decided against infiltrating their sanctuary.
It didn’t take long to find a more appropriate group, one counting doctors, scientists, and philosophers among its members. The Immortality Institute is a 501(c)(3) nonprofit educational organization whose mission “is to conquer the blight of involuntary death.” Members of the institute don’t see aging as a necessary reality: they see it as a disease. A curable disease. Or, to be more precise, “a sexually transmitted terminal disease that can be defined as a number of time-dependent changes in the body that lead to discomfort, pain, and eventually death.” To support the institute is to support research that will inevitably lead to eternal life. They all believe that science will ultimately orchestrate the defeat of death, and they’re trying to accelerate the process. Their forum boasts intricate debates about how exactly science will accomplish physical immortality. While surfing the site’s “events” section, I came across an open invitation from Dave Kekich, a registered imminst.org user.
If you want to celebrate the future, then come to my 125th birthday party on Saturday evening, May 23rd in Huntington Beach, CA. It’s a “Come as You Will Be Party.” Here’s the deal:
1. First, even though some people think I look it, I’m not nearly 125 . . . yet.
2. We are going to project ourselves to 2068 at the party.
3. You will act and speak as though it is 59 years from now. In fact, if you don’t agree to spend at least two hours “in character,” then stay home. There will be no 2009 discussions here unless you’re reminiscing. We will talk about what we’ve done and accomplished from 2009–2068, where we’ve been, what you’ve become, what changes the world saw in the past 59 years.
4. If you violate #3, you will be deposited into a worm hole in the basement which will immediately transport you back to where you came from.
The possibility of interviewing members of the institute in the flesh was tempting enough that I RSVP’d via e-mail: “Your 125th birthday party sounds like a wonderful idea! I’m a writer and I’d love to come. (I feel like it’s 2068 already).”
Soon, a response arrived from Kekich, with directions and elaborations about the theme:
Everything will be quite different 59 years from now. Since the power of our technology is doubling every year now with no end in sight (at least over the next 50 years or so), our tools will be over a thousand times more powerful in only ten years. If this doubling holds up over the next 59 years, that means our technologies, particularly our computational power, will be a billion billion times more powerful. Yes, that’s a quintillion, or 1 followed by 18 zeros. . . .
Imagine what America will be like, the world, the solar system. Aging? In my humble opinion, that solution will be a slam dunk. I believe we will have solved aging well before then.
Guests were asked to arrive in 2068-appropriate attire. It sounded perfect. I couldn’t wait to see how they lived—and partied.
Looking for advice on how to blend in with a crowd of extreme life-extensionists, I forwarded the invitation to Jenna Wright, a good friend and talented costume designer in Hollywood. “Are you into coming to an immortality dress-up party?” I wrote. “It takes place in the year 2068.”
“Are we supposed to be ourselves in 59 years?” she asked. “Or just anybody?”
“The theme is ‘come as you will be,’ but we can come however you’d like,” I responded, CC-ing Clay Weiner, a director who often collaborates with Wright.
“Silver bodysuits seem like a YES,” he replied.
My two wingmen offered to stop by a costume house to choose outfits for the three of us. “I’m thinking octogenarian leisure wear,” e-mailed Wright. “Possibly some new biomechanically engineered organs on display?”
From the forthcoming book "The Book of Immortality: The Science, Belief, and Magic Behind Living Forever" by Adam Leith Gollner to be published by Scribner, a Division of Simon & Schuster, Inc. Copyright © 2013 by 9165-2610 Quebec, Inc. Printed by permission.
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