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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 mecha
nism 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.
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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 th
e 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?
Book of Immortality Page 32
