Immortality Question: If you could live forever, would you and why? Answer: I would not live forever, because we should not live forever, because if we were supposed to live forever, then we would live forever, but we cannot live forever, which is why I would not live forever. --Miss Alabama in the 1994 Miss USA Contest Our attitudes toward aging and our responses to the changes in appearance that aging brings are totally colored by our knowledge that we are moving inexorably toward death. It is not my intention to write about death or the fear of dying in this book, but I find it impossible to avoid mentioning them as the source of our negative feelings about aging, which are entirely based in fear. Some species age more slowly than we do, others more rapidly. I have lived with dogs for many years and have watched several canine companions grow up, grow old, and die. As I write, I am looking at a photograph from several years ago of two of my Rhodesian ridgebacks on the front step of my house in southern Arizona. One is a young male, Jambo, who could not be more than a year old in the photo. He is standing--sleek, handsome, with all the vitality of youth. The other, B.T., must have been fifteen, very old for such a large breed. She is lying down, her face completely white. Soon she was unable to get up. I helped her through her decline but finally had to euthanize her a day before her sixteenth birthday. Jambo is now eight years old, still in his prime, still sleek, handsome, and vital, with a deep, soulful personality that makes him an ideal companion animal. Most people who meet him comment on how good-looking he is, the perfect combination of strength and beauty. Sometimes if I am reading in bed at night, I invite him to come up and sit beside me for a few minutes. If I rub his chest in a certain way, he looks up toward the ceiling, extending his neck in a posture of noble contentment that I find very appealing. But when he is in this position, I cannot avoid noticing the first white hairs on his otherwise black chin. And whenever I see them, I also cannot avoid noticing that there are more than the last time I looked. I know from experience that this dusting of white heralds the changes to come, that one day he, too, will be frosted with the white of old age; and when I see those signs of aging on his strong chin, I think about the disappearance of black from my own facial hair, about the unalterable passage of time, the relentless change of physical bodies as we decline. I think about the pain of the loss of previous companions, about separation from beings I love and who love me, about my own fear of the end and the sadness that is never separable from the joy of human experience. And all of this has come from the observation of a few white hairs on the chin of my dog. We all sense the finiteness of life, and we all fantasize about living forever. Is it any wonder, then, that we put so much effort into denying the fact of our aging with cosmetics, plastic surgery, and verbal deceits ("You look so much younger!"), and why we are so enthralled by proponents of antiaging medicine who tell us that we can stop or even turn back the clock? Immortality is an alluring concept, but I wonder how many of us have thought through its meaning and implications, which turn out not to be so simple. If you lived beyond the normal human life span, what would your life be like? I invite you to look at immortality with me through the lens of biology. Apart from framing this discussion of healthy aging, it will give you a chance to become acquainted with the latest findings of scientists who are studying the aging process. All of the practical advice I have to give you in Part Two of this book is based on this scientific evidence* and grounded in a philosophy that rejects immortality and eternal youthfulness as unworthy goals. A tension between mortality and immortality is played out on all levels of our being, from our cells to our psyches. Understanding it will help you accept the fact of aging and motivate you to learn to do it as gracefully as possible. ****************** Let's start with immortality on the cellular level. Until 1961, researchers believed that, in theory at least, normal cells, taken from the body and grown in laboratories, should be able to grow and divide forever if their needs were met: if they were provided with a constant supply of food and if their waste products were removed. In that year, Leonard Hayflick and Paul Moorhead at the Wistar Institute in Philadelphia demonstrated that this was not so, that all normal cells have a fixed limit on the number of times they can divide in order to replace themselves. This number is now known as the Hayflick limit. Hayflick, currently a professor of anatomy at the School of Medicine, at the University of California, San Francisco, is one of the foremost biogerontologists. His book How and Why We Age, first published in 1994, is the best I have found on the subject. I recommend it highly. It turns out that the Hayflick limit varies from species to species and often correlates with life span. With a Hayflick limit of about 50 cell divisions, humans are the longest-lived mammals. Mice, which live about three years, have a limit of 15 divisions; for chickens, with an average life span of twelve years, the number is about 25. At the extreme of longevity, the Galápagos tortoise, which can live for 175 years, has a Hayflick limit of 110. HeLa cells, however, can divide indefinitely. They do not senesce. They continue to grow and divide as long as they have nutrients, oxygen, space, and means of getting rid of their wastes. HeLa cells were the first human cells to be successfully cultured outside the body in large numbers. Given their longevity, they revolutionized biological and medical research and quickly established themselves in laboratories around the world. HeLa cells ignore the Hayflick limit for human cells. In a sense, they are immortal. I was taught that "HeLa" was composed of the initial letters of the name of a woman, Helen Lane, who was said to be the original source of the cells. This turns out not to have been true. The real source was Henrietta Lacks, a poor African-American woman from Baltimore, whose story only came out years after her cells were growing in prodigious numbers everywhere. Lacks was born to a family of tobacco pickers in Virginia, moved to Baltimore in 1943 at the age of twenty-three, married, and had five children in quick succession. Then, early in 1951, she noticed she had abnormal vaginal bleeding. She went to a clinic at The Johns Hopkins Hospital, where a doctor found an ominous-looking, quarter-sized tumor on her uterine cervix. He biopsied it and sent the tissue sample off for diagnosis. It was malignant. Shortly afterward, Lacks returned to the clinic to begin radium treatments, but before the first one, another tissue sample from the tumor was taken and sent, this time to George Gey, head of tissue culture research at Johns Hopkins. Gey, with his wife, Margaret, had been trying to find human cells that would grow well outside the body. His greater goal was to study cancer in order to find a cure. Henrietta Lacks's biopsy gave him exactly what he needed. Her cancer cells grew in test tubes as no other cells had ever grown, vigorously and aggressively. Of course, this did not augur well for their donor. Within months, Lacks's tumor had metastasized throughout her body, creating tumors in all her organs until she expired painfully in a racially segregated ward of The Johns Hopkins Hospital on October 4, 1951, eight months after diagnosis. On the same day, George Gey went on national television to announce his breakthrough in cancer research. He held up a vial of Lacks's cells, calling them, for the first time, HeLa cells. HeLa cells were soon in great demand. The Geys sent vials of them to colleagues, who sent them to other colleagues, and before long Henrietta Lacks's cancerous cells were multiplying in laboratories throughout the world. They made possible the development of the first polio vaccine, were used to study the effects of drugs and radiation, genetic mechanisms, and many diseases, and were even sent off the planet on a space shuttle to see how cultured human cells would grow in zero gravity. If the HeLa cells worldwide were added up, they would total many, many times the weight of the human being in which they originated. The saga of Henrietta Lacks raises uncomfortable ethical and social questions, because she never gave informed consent for her cells to be used in this way, neither she nor her family was ever compensated for their use (they did not even find out about all this until twenty-four years after the fact), and none of the scientists who worked with HeLa cells ever acknowledged her contribution. But that is another story. Why can HeLa cells go on living, perhaps forever, when the human being who produced them is long dead and when most cells senesce after a fixed number of divisions? What determines how many times cells from different organisms can divide? The answers are encoded in DNA, our genetic material. DNA is contained in rodlike structures called chromosomes in the nucleus of every cell. When cells are about to divide in order to reproduce and make more tissue, chromosomes have to replicate themselves, so that each daughter cell will have the same genetic information as its parent cell. The DNA spirals that comprise the chromosomes uncoil so that the genetic code can be copied to make duplicate strands, but each time this process occurs, something is lost: a piece of the end of each strand. Chromosomes terminate in a distinctive region of DNA called a telomere; the name comes from Greek roots meaning "end bodies." Telomeres have been likened to the plastic tips at the ends of shoelaces, but that is not an accurate simile, because there is no cap. Rather, the telomere is a repeating sequence of six "letters" (amino acids) of DNA code--TTAGGG--that might be translated in English as THEEND. This sequence repeats thousands of times in a young cell. The mechanics of DNA replication are such that a portion of the telomere is lost with each cell division. At the Hayflick limit, the length of remaining telomere is insufficient to allow further duplication of DNA strands to occur without serious genetic mishaps resulting. So there is no more cell division, no more reproductive life. Instead, there is senescence and, eventually, cell death. The discovery of telomeres and their possible relationship with the maximum life span of organisms has been one of the most important advances in the fields of genetics and biogerontology. It has allowed researchers to solve one of the great mysteries of cancer--namely, how cancer cells become immortal and go on dividing until they kill the organism in which they arise. In 1985, Drs. Carol Greider and Elizabeth Blackburn reported the discovery of telomerase, an enzyme that adds more six-letter units to telomeres, making up for their normal loss during cell division. They first found it in a microscopic one-celled animal called Tetrahymena that lives in freshwater lakes and streams and is commonly used in genetics research, but telomerase has since been found in many multicellular organisms, including humans. Although it almost never occurs in normal cells, most cancer cells produce it. Malignant transformation is a complex process involving the suppression of some genes and the activation of others, sometimes in response to carcinogenic agents, sometimes not. Malignant cells are unresponsive to general controls on growth and development and a threat to their normal neighbors, but it is a long way from malignant transformation of one or many cells to a clinically significant cancer with the potential to kill its host. Many cancer cells die because their genetics and metabolism are hopelessly deranged or because they outgrow their blood supply. Others are weeded out by the body's defensive systems. Those that survive will run up against the Hayflick limit--unless they acquire the ability to produce telomerase. A gene for telomerase expression is present in many cells but is inactive. (I will explain why it's there in a moment.) If a cancer cell manages to turn it on, and thus produce the enzyme to lengthen telomeres, it can divide indefinitely, giving rise to a clone of malignant cells that can eventually become a detectable tumor. This is what happened in Henrietta Lacks's cervix. HeLa cells owe their unlimited growth to telomerase. Telomerase expression is probably not the only path to cellular immortality, because 10 percent of tumors seem able to rebuild their telomeres without it; evidently, they find some other gene product to achieve the same end. As researchers close in on the fine details of cellular immortalization, new possibilities for cancer diagnosis and treatment may emerge. Detection of telomerase in tissue samples may announce the presence of cancer in its earliest, most curable stages. If we can find a way to suppress telomerase expression--to turn off the gene that controls it--we may be able to render cancer cells mortal again and stop their relentless growth. That may take too long to be a primary treatment, but it may be very useful as a backup approach to prevent metastasis, without the toxicity of conventional chemotherapy. *For the reader's convenience, a glossary of some of the scientific terms I employ appears after the text. Excerpted from Healthy Aging: A Lifelong Guide to Your Physical and Spiritual Well-Being by Andrew Weil All rights reserved by the original copyright owners. 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