It remains for us to discuss youth and age, and life and death. To come to a definite understanding about these matters would complete our course of study on animals.
—Aristotle, On Longevity and Shortness of Life, 350 BC
IN THE PAPER he wrote with Paul Moorhead, Hayflick had laid down a huge challenge to a half century of received wisdom that said cells in culture would keep dividing month after month and year after year, if only they were properly treated.1 He had gone even further in a 1965 paper by suggesting that normal cells’ lab-dish mortality might be related to the aging of whole organisms, including human beings.2
He met with plenty of push-back from the start. His findings were publicly challenged by Theodore Puck, the influential cell culturist whom the young Hayflick had stood up to question at that packed lecture in Atlantic City in 1961. “Sharp divisions were evident” between Puck and Hayflick about whether cells aged in culture, Science magazine reported from a 1965 meeting where Puck claimed that he had grown normal cells in culture through five hundred divisions without their dying.3 Like other noted biologists, Puck suggested that technical failures in Hayflick’s cell-culture methods were responsible for the cells’ deaths.4 Only time would definitively prove that Puck, whatever his eminence, was patently wrong. By 1974 the widely respected Nobel laureate Sir Frank Macfarlane Burnet allowed that “there is probably a majority opinion” that the lab-dish mortality that Hayflick had observed “measures an important biological quality of … cells which is significant for the interpretation of ageing.”5
Burnet coined the term “the Hayflick limit” to describe the number of replications that normal, noncancerous cells can undergo before they cease dividing. It took lasting root not only in science but also in popular culture. Today you can buy Hayflick limit T-shirts; the limit plays a role in the 2004 horror film Anacondas: The Hunt for the Blood Orchid; and it has inspired the naming of at least one garage band.
Hayflick’s findings opened a whole new field, the laboratory study of cellular aging. By the early 1970s the subject was enticing a growing number of biologists. In 1974 Congress created the National Institute on Aging as the newest among the cluster of research institutes that comprise the National Institutes of Health. (Congress launched the new institute in response to a relentless lobbying effort led by a wealthy Georgetown widow named Florence Mahoney. President Richard Nixon twice vetoed the bill establishing the new institute. He finally signed it when it was sent to his desk a third time, weeks before he was forced to resign in August 1974.)
Like others, Hayflick was drawn to the study of cellular aging and the raft of questions cracked open by his discovery. Was cellular aging in a lab dish simply the microequivalent of aging in human beings? What caused it? Was some essential factor that was needed for cell replication being depleted over time? Did cells age in lockstep, or were there individual differences between them? Were genes involved? How was it that the frozen fetal cells in his original experiments “remembered” their ages when they were thawed? Was there a different Hayflick limit for every species, and was it the number that one would expect, given the animal’s natural life span? The questions were endless.
Hayflick had tackled one of the most obvious and tantalizing of them in a 1965 paper that appeared in Experimental Cell Research, the same journal that had published his groundbreaking 1961 report. Did cells taken from adult humans—as opposed to fetuses—divide fewer times before reaching the Hayflick limit? From a colleague at the Mayo Clinic in Rochester, Minnesota, Hayflick obtained lung cells from the cadavers of eight people, ranging in age from a twenty-six-year-old who was killed in a car crash to an eighty-seven-year-old who died of heart failure. He found that they replicated far fewer times before growing old and ceasing to divide than had the thirteen lung-cell strains he had derived over time from human fetuses. The fetal lung cells ceased dividing, on average, after forty-eight replications; the eight adult strains petered out after an average of twenty divisions.6
It made intuitive sense, and yet his data showed that our cells don’t simply tick away toward the Hayflick limit on a predictable path as we age. The lung cells from the young auto crash victim doubled just twenty times in culture, while those from the eighty-seven-year-old who died of heart failure replicated themselves twenty-nine times before hitting the Hayflick wall.7 These cells from the most elderly lungs in fact doubled more times than the lung cells from any of the other seven cadavers, whose donors were aged mostly in their fifties and sixties when they died.
“There appears to be no exact correlation between the age of the [adult] donor and the doubling potential of the derived strain,” Hayflick wrote. Or if such a relationship did exist, “it cannot be detected by the present crude methods.” What was clear, he wrote, was the general observation that adult lung cells doubled far fewer times than their fetal counterparts before they ground to a halt in their cultures. Papers by other scientists over the coming fifteen years would establish definitively that a cell’s doubling potential did vary inversely with donor age, and that this was true for cell types as various as skin, liver, and the smooth muscle in the walls of arteries.8
Adding more complexity, a paper published in 1980 in Science showed that even which cells happened to have been randomly sliced from the lungs of those eight cadavers doubtless influenced Hayflick’s findings. That report, published by biologists James R. Smith and Ronald G. Whitney of the W. Alton Jones Cell Science Center in Lake Placid, New York, blew away any notion that cells within a tissue are identical, preprogrammed entities all marching rigidly toward a predetermined finish line.9 Smith and Whitney took a single lung cell from an aborted human fetus and, as it multiplied in culture, extracted one hundred or two hundred cells now and then. Then they tested each cell within that subgroup to see how many divisions it had left in it. They found a wide variation in the remaining doublings.
Digging deeper, they next took the two daughter cells that arose from the division of a single fetal lung cell and counted how many times the population of cells arising from each daughter was able to double itself. They did this over and over, beginning with many single cells. To their amazement, they found that the proliferative potential of the two daughter cells of each single cell was not identical and, in fact, varied by as many as eight population doublings.10 When it came to theories about what caused the Hayflick limit, “clearly, all current hypotheses should be reexamined in light of our data,” they concluded.
In the midst of the puzzlement, at least one thing had become clear, thanks to the efforts of Hayflick’s red-bearded graduate student, Woody Wright, the young biologist who was also completing an MD at Stanford’s medical school. In an elegant series of experiments under Hayflick’s oversight, Wright used a chemical called cytochalasin B, which he applied to WI-38 cells in culture. At high doses the chemical ejected the nuclei from the WI-38 cells, resulting in WI-38 cells dubbed cytoplasts, full of cytoplasm but without nuclei.11 Separately, Wright treated normal WI-38 cells with a different pair of chemicals that inactivated a broad range of components in their cytoplasm. Then he fused the nucleus-free cytoplasts—which still had functioning cytoplasm—with the WI-38 cells that still had nuclei.
This allowed for a series of mix-and-match experiments in which Wright created cells with young nuclei but old cytoplasm; young nuclei and young cytoplasm; old nuclei and young cytoplasm; and old nuclei and old cytoplasm. With each kind of hybrid he watched to see how many more divisions occurred before it hit the Hayflick limit and stopped dividing. If the control seat of cellular aging was in fact in the cytoplasm, then the hybrid WI-38 cells with “young” cytoplasm should live much longer than those with “old” cytoplasm, regardless of the age of the nucleus. But if the control seat of cellular aging was in the nucleus, then the cells with younger nuclei should live longest, regardless of the age of the cytoplasm. The latter is what Wright found.
His experiment was published, with Hayflick as coauthor, in 1975, as Wright completed his MD and PhD and launched a long career pursuing the mysteries of aging.fn1 12
He had aptly demonstrated that whatever was controlling the number of cell doublings in normal diploid cells like WI-38 was located in the nucleus and not in the cytoplasm. Years later Hayflick would dub this whatever-it-was a “replicometer.”13 As distinct from a clock, which measures time, the replicometer measured replications. When a cell wasn’t replicating—for instance, when it was in the freezer—the replicometer stopped chalking up replications.
That the replication-counting mechanism resided in the nucleus wasn’t surprising. The nucleus was known to govern myriad important functions of cellular life. But locating the mechanism and understanding it were two vastly different projects. How it was teased out is one of the great stories of late-twentieth-century biology, because it shows how profound findings with huge implications for human health can emerge from the unlikeliest of organisms, the depths of basic biology, the powerful engine of scientific curiosity, and the cross-pollination that happens when scientists share ideas. It also connected Hayflick’s iconoclastic observation in the early 1960s with the discoveries that would lead to a Nobel Prize for others nearly fifty years later.
In 1938 the Nobel Prize–winning American geneticist Hermann Muller described what seemed like protective caps of DNA located at the ends of chromosomes, something like the bits of plastic banding that cap the ends of shoelaces to keep them from fraying. He named them “telomeres,” from the Greek telos + meros, meaning “end part.”14 Three years later another great American geneticist, Barbara McClintock, who would also win a Nobel, described a crucial role for telomeres in maintaining the integrity of chromosomes.15
Both biologists worked with broken chromosomes, and both noted that chromosomes in their natural state had ends that were somehow protected from the abnormalities that occurred at unnatural chromosome breaks induced by radiation or rupture. Their tantalizing observations sat unexplained for most of the next forty years. There simply weren’t the tools available to probe them further.
The revelation of the molecular structure of DNA by James Watson and Francis Crick in 1953 began the stepwise process that would produce those tools. It was soon followed by the discovery of a vital enzyme by Arthur Kornberg—one of the “Bergs” whose reputations drew Hayflick to Stanford. Kornberg described DNA polymerase—the enzyme that duplicates a cell’s DNA in preparation for cell division—and teased out how this essential enzyme works, by attaching itself to a long strand of DNA and moving along its length, transcribing the letters of the DNA alphabet as it goes. Kornberg won a Nobel Prize in 1959 for his discovery.
One autumn evening in 1966, a young Russian biologist had a flash of insight that linked Kornberg’s all-important enzyme to the Hayflick limit. Alexey Olovnikov was a postdoctoral student at the Gamelaya Institute of the Academy of Sciences of the USSR. He was on his way home from a lecture at Moscow University on the radical new findings of the American scientist Leonard Hayflick. “I was simply thunder-struck by the novelty and beauty of the Hayflick Limit,” he later wrote.16
Mulling what he had heard, Olovnikov descended into the subway. As he stood on the platform and heard the roar of an approaching train, he thought in a flash that the tracks made an apt analogy to DNA and the train running along them to DNA polymerase, the enzyme that copies DNA in preparation for cell division by traveling along the length of the DNA in a chromosome, making a new copy as it passes. But just as there was a “dead zone” between the front of the train and the first passenger door—“dead” because the whole purpose of the train was to carry passengers—perhaps there was a dead zone at the very tip of the chromosome that DNA polymerase couldn’t copy, although the enzyme’s entire purpose was to copy DNA. If this was true, a cell’s genome—its instruction book for a life—would be slowly shortened through the multiple cell divisions of a lifetime, with DNA at one end of its chromosomes getting lost bit by bit, copy by copy. A railway that kept losing track was untenable.
Olovnikov spent the next four years thinking about the Hayflick limit and developing his theory as he rode the Moscow subway to and from work, waiting for the approaching train in the same subway station where he had his epiphany. He finally published his theory in Russian in 1971.17 He proposed that DNA polymerase could not copy the DNA at one end of each chromosome, so that chromosomes were inexorably shortened with each cell division. But he added that the DNA at the ends—the telomeres, that is—might be expendable, not spelling out any information that was vital for the life of the cell. If so, the DNA of the telomeres could be sacrificed, chopped down bit by bit, replication by replication, while the important DNA—the DNA that directed the life of the cell—survived intact.18 Telomeres, in other words, played a buffering role. But they were finite buffers. Buffers that could be shortened and shortened until, when the last bit of telomeric DNA was reached, so was the Hayflick limit. Because the cell at this point could no longer replicate without eating into its life-directing DNA, it would stop dividing. Olovnikov also conjectured, presciently, that cancer cells might have a mechanism allowing them to escape this telomere shortening, making them immortal.19
In the Western-dominated world of science, Olovnikov’s theory remained all but invisible, even after an English translation was published in 1973.20 However, the theory that the copying enzyme, DNA polymerase, could not replicate that troublesome end bit of the chromosome was separately described in 1972 by James Watson, the American scientist who had twenty years earlier discovered the structure of DNA with Francis Crick.21 While Watson did not make the connections to the Hayflick limit and cancer that Olovnikov did, his paper nonetheless put on the map the phenomenon that became widely known as the “end replication problem.”
Olovnikov’s ideas were, in any event, theoretical when he published them. They were not corroborated by any experimental evidence. The quest that would produce that evidence—and a Nobel Prize almost four decades later—was led by a trio of American scientists: an ambitious Californian graduate student with dyslexia; an exuberant, cerebral daughter of Australian doctors; and a competition-averse Canadian migrant to Boston.
Elizabeth Blackburn had been fascinated with the natural world from her earliest days growing up as the child of physicians in Tasmania, when she used to hold and even sing to jellyfish that washed up on the beach.22 In the mid-1970s, as a postdoctoral student at Yale University, she began working with Tetrahymena thermophila, a single-celled, pond-dwelling organism that is covered with fine, hairlike projections called cilia. Tetrahymena are a favorite of research scientists because they are cheap, they grow rapidly, and they engage in many of the cellular processes common in more complicated organisms, like humans. Most important for Blackburn, Tetrahymena have a multitude of mini chromosomes. This provided plenty of material for her studies of telomeres, whose function had mystified scientists for decades, and which also captivated Blackburn.
She set out to determine the letter-by-letter sequence of Tetrahymena telomeres. While gene sequencing was a new tool at the time, Blackburn was ideally placed to use it—she had learned the technique from its pioneer, Nobel Prize winner Frederick Sanger, with whom she completed her PhD at Cambridge University. The paper she produced was coauthored by Joseph Gall, her mentor at Yale—although it was published in 1978, the year that Blackburn became an associate professor of molecular biology at the University of California at Berkeley. It showed that the ends of Tetrahymena chromosomes contained a short sequence of six letters of DNA code—CCCCAA—that was repeated over and over, from twenty to seventy times.23 Her discovery was groundbreaking. No one had described the molecular structure of the chromosome tips in any species. Soon scientists were sequencing the telomeres of other simple organisms and finding that these too consisted of short DNA sequences repeated many times over at chromosome ends.
Across the country in his lab at the Sidney Farber Cancer Institute in Boston, a young Harvard Medical School professor named Jack Szostak had been struggling to understand how a very different single-celled organism, the humble baker’s and brewer’s yeast, handled broken bits of DNA. When Szostak inserted linear, lab-manufactured DNA strands, unprotected by telomeres, into the yeast, the DNA was either inserted into a chromosome or completely destroyed. Or, occasionally, the two ends of a strand would be joined together to form a circular bit of DNA. Szostak’s pieces of DNA never survived as linear strands, for unlike naturally occurring chromosomes, their ends weren’t protected by telomeres. Then Szostak heard Blackburn discuss her work at a conference in the summer of 1980. He approached her, and during an intense discussion the pair came up with what Szostak later recalled as a “wild idea.”24 They would graft Tetrahymena telomeres onto the end of Szostak’s lab-created mini chromosomes and insert them in yeast. Just maybe the grafted-on telomeres would protect Szostak’s chromosomes.
Blackburn and Szostak found their long-shot hunch confirmed. The mini chromosomes with their grafted-on telomeres were not degraded. Somehow that six-letter repeating sequence of DNA in the Tetrahymena telomeres was protecting the chromosome ends, even in a very different organism. (It’s now known that in humans and other mammals the specific DNA sequence of telomeres attracts a group of proteins—appropriately named “shelterin”—that form a cap at the fragile chromosome end, preventing the cell from “thinking” that it is an open, broken end and trying to repair it, a process that can end in cell suicide if the repair work fails.)
Blackburn and Szostak published their findings in the eminent journal Cell in 1982.25 Now another question presented itself. The end-replication problem dictated that the yeast telomeres should get shorter and shorter with each division, until they were gone and essential DNA began to be lost. In a single-celled organism, this wasn’t compatible with survival. An organism of just one cell, like yeast, had to be able to replicate infinitely, or perish. Such organisms must have some mechanism for fighting back against the end-replication problem. Soon after, working with Blackburn’s graduate student Janis Shampay, Blackburn and Szostak demonstrated that in yeast the telomere ends were being extended with additional tiny DNA snippets while they replicated.26 In effect, the cells seemed to be “trying” to maintain their telomeres at a roughly constant length.
The scientists proposed that there might be an enzyme capable of lengthening chromosomes at their tips by adding those small, repetitive snippets of DNA. This enzyme would have to work quite differently from DNA polymerase, the powerful enzyme that replicated the whole of a cell’s DNA during cell division—except for that troublesome end bit—but which required a DNA template from which to copy.
On Christmas Day 1984 Carol Greider, a twenty-three-year-old PhD student in Blackburn’s Berkeley lab, peered at a newly developed X-ray film and saw something that seemed like it was too good to be true.27 It was the first hard evidence that a telomere-lengthening enzyme existed. It showed up in a series of neat bands that climbed, ladderlike, up the X-ray film. The regularity of the bands made it clear that the putative enzyme was adding six-base snippets of DNA—telomeric repeats—to the telomeres in a test-tube mix that Greider had made, containing synthetic telomeres and extracts of Tetrahymena cells.28 (After further experiments confirmed that her seemingly too-perfect findings were in fact real, Greider went home and danced to the whole of Bruce Springsteen’s Born in the U.S.A.)
It would be 1990 before Blackburn and her colleagues at Berkeley definitively demonstrated the enzyme’s activity in a living organism.29 By then it had been given a name: telomerase. It was a complicated, unusual enzyme, and Greider and Blackburn had shown that it carried its own template of genetic code, allowing it to affix itself to the end of the chromosome—the bit that DNA polymerase can’t manage to duplicate—and begin adding genetic sequence in the form of the telomeric repeats specific to that species.30
How does all of this circle back to Hayflick’s fibroblasts aging in their bottles half a century ago? It would take a conversation between Greider and a scientist named Calvin Harley, at McMaster University in Hamilton, Ontario, to finally connect those dots. Greider often traveled from Berkeley to McMaster to visit her boyfriend, Bruce Futcher, who shared a lab with Harley, a mustachioed, mild-mannered Canadian who had been fascinated with aging since he was a boy.31
It was Harley who told Greider about an obscure theory that she had never heard of. It had been proposed back in 1971 by a young Russian who had an epiphany in the Moscow subway. Greider learned about Alexey Olovnikov’s theory that cells hit the Hayflick limit because of the end-replication problem—the cells finally stopped dividing when they somehow discerned that more divisions would begin to eat into their critical, life-directing DNA. Olovnikov had not had the tools to test his theory almost two decades earlier. But in 1988 the human telomere sequence—TTAGGG—was discovered.32 Greider, who had completed her PhD and taken a position at the Cold Spring Harbor Laboratory on Long Island, New York, heard of the discovery early, at a conference, and called Harley with the news. She, Harley, and Futcher now had the means at hand to find out if Olovnikov had been right. They could ask and answer the question: what happens to the length of human telomeres over time?
They grew fibroblast cells that had been derived from several types of human tissue: fetal lung tissue; newborn skin; and skin from adults aged twenty-four, seventy-one, and ninety-one years. As the cells replicated, the scientists regularly measured the length of their telomeres. No matter what their starting lengths—and the fetal and newborn cells had substantially longer telomeres to begin with—all of the cells’ chromosome tips grew progressively shorter with time. On average their telomeres were clipped of two thousand DNA letters before they died, or roughly fifty letters each time the cells divided. The findings comported beautifully with the end-replication problem and left the cells with, on average, about two thousand letters in their telomeres when they finally stopped dividing—an amount, the scientists inferred, that could be merely a nonfunctional stub. Their findings “could be biologically significant,” the three biologists wrote, with typical scientific restraint, in the 1990 Nature paper that reported on the experiment.33
Why didn’t telomerase “save” the cells in this experiment, protecting their telomeres by adding to them to maintain their lengths? The answer had to be that telomerase was not active in all human cells. And in fact other scientists would soon demonstrate that telomerase is lacking in most human cell types.
With the publication of the Harley-Futcher-Greider paper, a simple, elegant concept captured the public imagination: telomeres in effect burn down, like a candle wick, until the end is reached, the light goes out, and the cell stops dividing and, finally, dies. The notion was a tantalizing and seductive one, not least for questers after the fountain of youth. For it wasn’t unthinkable that what happened in a test tube might happen in the human body: that the ravages of growing old, from sagging skin and thinning hair to all manner of age-related diseases, resulted from the clipping down of our telomeres; and that telomerase might rescue humanity from all of that. That notion, Blackburn later told the writer Stephen Hall, “was a lovely idea—so simple that nobody but an idiot would believe it.”34
This did not dissuade the enthusiastic. In 1990 a company called Geron was established in Menlo Park, California, to chase the promise of telomerase in battling aging. The scientists at Geron were keenly aware that Harley, Futcher, and Greider had demonstrated a correlation between telomere shortening and cellular aging but that, as the trio themselves pointed out, their findings did not establish that the shrinking telomeres caused cells to become elderly. A few years later the Geron scientists, working with Hayflick’s former graduate student Woody Wright and his group at the University of Texas Southwestern Medical Center at Dallas, conducted an experiment designed to reveal whether telomere shortening caused cells to age. They added telomerase to two kinds of cells: fibroblasts from human foreskin and from specialized cells that line the retina in the human eye. They also kept control cultures of each of these cells, without telomerase added.
The control cells proceeded to divide to their Hayflick limit, take on the appearance of elderly cells, and stop dividing. Those with the telomerase did not. On the contrary, they flourished, maintaining long telomeres, dividing prolifically well beyond their Hayflick limit, and yet maintaining normal chromosomes; these were not cancer cells that had somehow bypassed the normal brakes on cell division. By the time the resulting paper went to press, the telomerase-rich cells had exceeded their normal number of replications by at least twenty doublings. The scientists had established beyond doubt a causal relationship between telomere shortening and the aging of cells in the lab. The new paper, published in Science in 1998, had an eye-grabbing title: “Extension of Life-span by Introduction of Telomerase into Normal Human Cells.”35
A media frenzy followed. The New York Times splashed the news on its front page, then ran two more articles in the space of six days.36 “I didn’t think I’d live long enough to see this,” Hayflick told the San Francisco Chronicle in another front-page article.37 The price of a share in Geron rose from $7.80 on the last day of 1997 to $12.70 on January 16, 1998, the day the Science paper was published. Twenty months later, as the price still hovered around $11.00, Fortune observed that “the bold little company has achieved the highest buzz-to-equity ratio in biotech history.”38 But the story turned out to be commercially disappointing. In the summer of 2016 the twenty-six-year-old Geron had yet to win FDA approval for a single product and had abandoned its attack on aging for an attack on cancer. Its stock was trading at less than $3.00 per share.
The relationship between telomeres and aging has emerged as immensely complex. The running-down of telomeres in cells in the lab does not translate as the simple, unitary cause of the aging of entire organisms, including human beings. For one thing, unlike cells in culture that grow to their Hayflick limits and then stop dividing, most of the cells in our bodies divide rarely. These cells probably do not come close to running down their telomeres in the course of our life spans—something that Hayflick’s work with those specimens from multiaged cadavers back in 1965 pointed to quite clearly. (Remember the lung cells from the eighty-seven-year-old cadaver that divided another twenty-nine times in culture?) What’s more, we now know that the aging of our cells is also likely mediated by mechanisms that can bypass telomeres entirely, like chronic inflammation and something called oxidative stress, in which toxic by-products of cellular metabolism directly damage proteins and other cell components.
Nonetheless, a group of patients with rare, inherited genetic disorders have provided important evidence of a direct effect of telomere length on aging in living human beings. People with these disorders, which have been collectively dubbed “short telomere syndromes,” have very short telomeres and suffer from a characteristic set of age-related degenerative diseases.39 Often these diseases make themselves manifest in cells that, unlike most, divide frequently, like the stem cells in organs that repair and maintain them in the face of wear and tear, or the stem cells in bone marrow that give rise to billions of blood cells each day. For instance, one disease that appears in people with short telomere syndrome is aplastic anemia, a condition in which the blood cell–manufacturing cells in the bone marrow fail and the numbers of all kinds of circulating blood cells fall dangerously low.40
Is the converse then true? Do long telomeres bode well for health? Some tantalizing findings have suggested as much. One particularly striking study of scores of healthy centenarians showed that both they and their offspring maintained longer telomeres as they aged, compared with subjects of ordinary longevity. It also showed that longer telomeres were associated with better mental functioning, healthy levels of blood fat, and fewer age-related diseases.41 However, this study did not establish cause and effect. It simply showed a correlation.
Importantly, telomerase has been implicated in cancer. The scientists at Geron—along with other groups working elsewhere—showed that in stark contrast to most normal cells, telomerase is active in cancer cells. Working with Wright and his colleague Jerry Shay at the University of Texas Southwestern Medical Center at Dallas, they measured telomerase activity in 101 biopsies from human cancers and in 50 biopsies from normal human tissues. Telomerase was active in 90 of the cancer samples and none of the normal ones.42 After their paper was published in Science in 1994, research on the role of telomerase in cancer skyrocketed.43 Recent findings include several papers showing that in families with inherited mutations that kick telomerase into high gear, the risks of malignant melanoma (a skin cancer) and of glioma (a brain cancer) are elevated.44 Biologists have also found evidence that a cell’s ability to shut down its own division—to short-circuit itself into a post–Hayflick limit, nondividing state—may have evolved as an essential defense against cancer.
Like the complex role of telomerase in cancer, the relationship between telomere shortening and aging is still being studied intensively today. We now know that there are a variety of influences, internal and external, on telomere length that make it clear that telomeres aren’t like wind-up clocks that start ticking when we are in the womb and march in lockstep toward a predictable, predetermined finish line. Heredity plays a role: some of us have the good fortune to inherit longer telomeres than the average human being. So do environmental exposures.
Today biologists are probing basic questions like these: What exactly tips telomeres from being dangerously short into being nonfunctional? What precisely happens to them, at the molecular level, as they hit the Hayflick limit? And when this happens, what complicated symphony of cellular signaling actually causes the cell to stop dividing? Each new answer they find opens up an ever-deeper set of questions.
In December 2009 in Stockholm, King Carl XVI Gustaf of Sweden presented Blackburn, Greider, and Szostak with the Nobel Prize in physiology or medicine for their discovery of how chromosomes are protected by telomeres and of the enzyme telomerase.
Hayflick had described a phenomenon. The Nobel trio had explained it.