| The Magazine of the CALIFORNIA ACADEMY OF SCIENCES |
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Counterpoints in Science Aging, Terminable and Interminable
How can we live for a hundred years or longer and yet avoid all the miseries of old age? Researchers tend to look at aging on three different levels: the population, the individual, and the cell. Population statistics show long-term trends in survival and mortality. Physicians study the diseases of aging in individual patients, and clinical trials test the value of regimes such as aspirin, diet, or exercise in selected groups of individuals. On the cellular level, researchers have been looking into the genes and molecular mechanisms that affect aging and longevity. Rapid changes are occurring on all three of these levels, with potentially dramatic consequences for individuals and society. Due to antibiotics and other medical advances, mortality in the United States has declined steadily during the past century, especially in women. The annual death rate per thousand females has descended almost to zero. Presenting this information in a lecture last summer, I joked that pretty soon American females would become immortal. I didn’t really believe this, of course. But to my surprise, in the July 2002 issue of the journal BioEssays, six eminent researchers on aging, headed by Aubrey de Grey of the University of Cambridge, argue that within a decade or two it may be possible to extend the lives of both women and men indefinitely. These scientists don’t write that they would be creating eternal life. That’s a loaded phrase with too many metaphysical overtones. A new triple-speak term has been coined for this startling contingency—engineered negligible senescence, or ENS. Has this millennial fantasy, a central subject of religion, philosophy, and literature, finally become feasible? During the past few years, genetic engineering has nearly doubled the lifespans of model organisms such as the nematode worm and the fruit fly. With mammals like mice, however, genetic manipulation has been much less successful. The only proven strategy for increasing mammalian lifespan significantly is caloric restriction, and living longer isn’t much fun if you are always half-starved. A. de Grey and coauthors contend that slowing the aging process is not the way to go. They believe it may be easier to reverse aging than to retard it. According to these investigators, aging is mainly due to the toxic side effects of our metabolism. Oxygen, which is essential for many life forms, can damage protein and DNA molecules. Scientists have found a gene in fruit flies that counteracts this damage by mopping up “free radicals,” metabolic byproducts of oxidation that attack tissue. By giving fruit flies an extra copy of this native gene, researchers can greatly prolong the life of these tiny insects. Stem cells can replace aging bone marrow, and, potentially, other organs such as failing hearts and kidneys. Interventions that reverse aging are far from perfect, but they are improving all the time. The BioEssays article presents a chart showing that the age of the oldest person in Sweden increased from 101 to 108 years between 1860 and 1969, about half a year each decade, and from 108 to 111 between 1969 and 1999. That’s about a year for each decade, and the rate is still rising. To achieve ens, the rate would have to increase to one year per year; that is, one year of life added for every year of life lived. Extrapolating the present line of increase, it looks as though death-defying ENS might be achieved around 2020. At that point, people will have attained an “anti-aging escape velocity,” where aging is postponed by successive medical advances faster than time is passing. Many of us have a “yuck” reaction to this prospect. In America, old age is held in low esteem, so why drag it out? In Greek mythology, Tithonus prayed for eternal life and was punished by the gods with unending miserable senescence. That’s what we all worry about when we think of growing very old. Most of us would like to live only as long as we can remain reasonably healthy, active, and alert. A. de Grey and his five colleagues don’t provide the formula for maintaining one’s wits and capacity for joy in extreme old age. They recognize this is a serious drawback to ens. Fortunately, there is some evidence that it’s possible for human beings, as well as worms and flies, to senesce gracefully. Aging Well, by George Vaillant (Little Brown & Co, 2002) describes the longest study of aging in the world. Now in its sixth decade, Harvard’s Study of Adult Development deliberately set out to study the well, not the sick. Three different groups, a total of 824 individuals, were selected as teenagers more than half a century ago so that researchers could study different facets of mental and physical health; they ended up being studied for their entire lives. The first group consisted of 268 socially advantaged Harvard male sophomores born about 1920. The study was criticized for looking only at the elite, so a second group was added—456 socially disadvantaged inner-city male teenagers born about 1930. Next the study came under fire for not including women, so a third group was added—90 middle-class California females, born about 1910, who had participated in an educational program for “gifted children” run by Lewis Terman of Stanford University. The Harvard Study of Adult Development assesses physical health, psychosocial health, and death. Obviously, death is the easiest criterion to score. Every five years the survivors have an intensive examination and interview. An internist rates them on a scale of one to four from healthiest to least healthy, taking into consideration both the objective measurements of the examinations and the subjective reports of the individuals and their families. One can be young or old for one’s chronological age. Physical health also involves experiencing the ravages of age without feeling “sick.” Good self-care, high morale, intimate friends, and mental health make the difference between “being ill” and “feeling sick.” Presidents Roosevelt, Kennedy, Johnson, and Eisenhower suffered illnesses that would have merited a 100 percent disability rating from the Veterans Administration, but nobody, including themselves, would have called them sick. Vaillant writes, “Clearly, subjective health is as important to aging as objective physical health.” He reports that, in general, successful adolescence predicted successful old age. “I was astonished at how much of a septuagenarian’s healthy aging or lack of it is predicted by factors already established before age 50. What seemed even more astonishing was that these factors are more or less controllable.” The study observed seven factors that predicted healthy aging: not smoking; not abusing alcohol; not being overweight; exercising; having a mature coping style (being able to turn lemons into lemonade rather than molehills into mountains); having a stable marriage; and a high level of education. The number of years of education correlate with improved self-care and healthful habits. The good news, according to Vaillant, is that most of us—if we start young and try hard—can voluntarily control our weight, our exercise, and our use of cigarettes and alcohol. “Whether we live to a vigorous old age lies not so much in our stars or our genes as in ourselves,” he says. Perhaps more surprising than the seven factors that did correlate with healthful aging are six factors that did not: ancestral longevity; stress; parental characteristics; childhood temperament; ease in social relationships; and cholesterol at age 50. None of these distinguish the Happy Well from the Sad Sick or even from the Prematurely Dead. Stress in particular has been thought to shorten or impair the quality of life, but symptoms of stress before 50 did not correlate with health at 75. Vaillant speculates that over the decades, people recover from the effects of stress. Vaillant also observes that to have a full old age and an enjoyable retirement, you must keep on learning all your life. Gusto for education in late life is highly correlated with psychological health. The capacity to take a fresh look at things makes a young person out of an old person. Lifelong learning was a characteristic of most of the successful agers in this book. I teach a course at the Fromm Institute for Lifelong Learning at the University of San Francisco, and my students, retired men and women over 50, also encourage optimism about growing older. Coming back to the question of what’s likely to happen to those who live beyond their eighties, the Harvard Health Letter 27 (Jan 2002) addresses the topic “Living to 100: What’s the Secret?” In the United States, the number of centenarians doubled in the 1980s and again in the 1990s. The total now exceeds 70,000 and by 2050 could be over 800,000. One of the rewards of living a long life is that, for the most part, the extra years are healthy ones. Generally, people who live to 100 exercise their bodies and their brains; they are walkers, bikers, and golfers; they read, paint, play musical instruments; some even continue to work. They maintain close ties with family and friends. By age 102, two-thirds suffer from some kind of dementia, but the period of serious illness and disability tends to be brief. Gerontologists call this “compressed morbidity” and compare it to the Wonderful One-Hoss Shay in a poem by Oliver Wendell Holmes: a carriage built so carefully that no single part breaks down for 100 years; then it collapses “all at once and nothing first, just as bubbles do when they burst.” If the program of engineered negligible senescence (ens) is to be a blessing rather than a curse, it must not only use genetic and medical interventions to extend life, but apply the knowledge that comes from long-term studies of real humans to extend meaningful life. Old age is not necessarily a drag, as our youth culture makes it out to be. A distinguished novelist who was one of the Harvard Study subjects wrote: “Contrary to all expectations, I seem to grow happier as I grow older. I think that America has been sold on the theory that youth is marvelous but old age is a terror. On the contrary, it’s taken me 60 years to learn how to live reasonably well, to do my work and cope with my inadequacies. For me, youth was a woeful time—sick parents, war, relative poverty, the miseries of learning a profession, a mistake of a marriage, self-doubts, booze, and blundering around. Old age is knowing what I’m doing, the respect of others, a relatively sane financial base, a loving wife, and the realization that what I can’t beat I can endure.” Now, that makes a lot of sENSe. Jerold M. Lowenstein is professor of medicine at the University of California in San Francisco. jlowen@itsa.ucsf.ed |
