By Mary Batten - author of The Tropical Forest, has also written films Science writer-editor Stephanie Bernardo helped research this article.
Science Digest February 1984
Meet Jeff, an average male baby born in 1983. Even at his tender age, Jeff has already started to “age.” At conception, the egg that produced him had already begun to break down because it was 35 years old-the age of Jeff’s mother, who, like all women, was born with all the eggs she would ever possess. And when Jeff reaches puberty, his thymus gland, which controls his vital disease-fighting system, will begin to shrink steadily until it almost disappears in old age.
Changes, or involutions, such as this occur painlessly and invisibly. But such changes many of which will continue gradually throughout Jeff’s life-are what we know as “ageing.”
Today scientists are trying to determine why these changes take place, how they can be prevented and if they can be reversed. For most species of animals, whose daily lives hang in an environmental system of checks and balances, life is as philosopher Thomas Hobbes predicted: “nasty, brutish and short.” And, from an evolutionary point of view, death at an early age is inevitable and desirable for most species, so that only the fittest will survive to mature, reproduce and rear their young.
Mankind, however, does not always abide by the dictates of the so-called natural order. In our grandiosity, we propose to change nature and extend life. “And why not?” ask some scientists.
Less than 50 years have elapsed since penicillin drugs became widely available. Only 20 years have passed since Francis Crick announced that he and James Waitron had “discovered the secret of life” by unravelling DNA, the basic ingredient of the genes, which may ultimately yield the mysteries of disease and ageing. With the rapid strides that have taken place in the fields of molecular biology and pharmacology, we have been given hope to dream of a longer life. Might we also, one day, dream of the immortality we have sought since the beginning of time?
Every species has a characteristic life span-3 years for a mouse, 45 for a chimpanzee, 60 for an elephant. And some organisms are astonishingly long-lived. The scraggly bristlecone pines in California have lived almost 5,000 years; they are older than the pyramids. Desert creosote bushes have been around for 10,000 years, having sprouted about the time our hunter-gatherer ancestors in the Middle East were discovering the advantages of a settled agriculture.
But for every living thing, ageing is a factor even before the moment of conception. Ageing in the human egg may cause Down’s syndrome and other chromosomal birth defects that occur with increasing frequency in the children of women who give birth after 35. Advanced age in father seems to play a part in some cases of progeria a rare disease (there have been only 60 recorded cases; that dooms children to old age before they reach puberty. Even in infancy their tissues and organs age, and their skin wrinkles. Most die of a heart attack by the age of 10.
THIRTIES: Passing the physical peak. After age 30, the functional capacity of the body will decline by about 0.8 percent each year. # Heart muscle starts to thicken. Hearing begins to decline (it peaked at age 10). # Skin is losing Its elasticity; frown lines and smile lines begin to appear. # At 30, the musculature is still Intact, but the disks in the vertebral column are deteriorating and causing bones to move closer together; the back will begin to slump after this decade. # Sexually, a woman reaches her peak.
Unfortunately, paediatricians can’t do anything to help progeria victims, because there is no cure for old age in children or adults-at least not yet.
Throughout history, humans have dreamed of antidotes to ageing and have considered using the breath of virgins, the blood of gladiators, turtle broth, gold liquor and transfusions of owl’s flesh. In 1492, Pope Innocent VIII tried drinking blood from three young donors, but he died shortly after the treatment.
In 1889, Charles Edouard Brown-Se’quard, 72, a onetime Harvard professor, injected himself with le liquide testiculaire from dogs and guinea pigs. Though it didn’t retard his ageing, his ideas ultimately led to hormone treatments that have been used to delay menopause and to forestall other effects of ageing.
Before World War II, Dr. Serge Voronoff, a Russian-born surgeon, declared that the monkey was “a warehouse of spare parts for the whole human body,” and he transplanted ape testes into 2,000 patients.
Today, many researchers believe that ageing is controlled by genes and that our bodies are programmed to decay. Back in the 1960s, Leonard Hayflick, now director of the Centre for Gerontological Studies at the University of Florida, hypothesised that each cell had a genetic clock ticking away and that cells would divide no more than 50 times. But the “Hayflick limit,” as it came to be known, was disproved in 1972 by David Harrison, now senior staff scientist at the Jackson Laboratory in Bar Harbor, Maine. He took stem cells (which come from bone marrow and mature into the red blood cells that carry oxygen in the blood) and transplanted them from old mice into young mice whose bone marrow had been destroyed by radiation. After the young recipient mice grew old, he transplanted the original stem cells into a new set of irradiated young mice, and so on. He found that stem cells from the first group of old mice survived through four or more generations.
“If Hayflick had been correct,” says Harrison, “when you transplanted stem cells from old mice into young ones you should see a real difference in their functioning after a point. But we didn’t see this. Stem cells don’t seem to age.”
Other researchers believe that we age because our bodies are damaged by disease and “free radicals,” highly unstable molecules with an extra electron that are a by-product of metabolism. One of the foremost authorities on ageing, Roy Walford of the UCLA Medical School, calls free radicals “the great white sharks of the biochemical seas.” Most of them are oxidising agents that damage membranes and DNA, just as oxidation outside the body can damage-rust iron. Our protection lies in enzymes that break down, or scavenge, the free radicals. New evidence indicates that the gene family that controls ageing also regulates some of the helpful scavengers. As we get older, however, the accumulated damage our bodies have received from the white sharks and from disease may begin to produce decay.
FORTIES: Beginning the decline. A 40-year-old man is probably carrying 10 or 20 pounds more than he did at age 20 and stands about one-eighth of an inch shorter. The body’s natural defences are beginning to wane. Lymphocytes show a marked decrease in the killing power against cancer cells. Other Infection-fighting cells grow less effective. # Hair Is greying and balding may begin. The diameter of hair follicles has thinned by about 2 microns. By the time most men are in their late 40s they will be farsighted.
To date, no one has discovered one central clock that ticks off our life span in the genes or anywhere else. Instead, ageing seems to be influenced by three different but interrelated systems: (1) the brain; (2) the endocrine system, which secretes hormones; and (3) the immune system, which manufactures an awesome array of antibodies and natural drugs, such as interferon.
As the brain grows old, it doesn’t appear to deteriorate. Researchers think the brain’s neurones could last 150 to 200 years if their bodily support systems didn’t fail. (Loss of hearing at high frequencies, which occurs commonly in older people, comes from changes in the ear itself, not in the brain.) The number of nerve cells in the brain arrives at a plateau, explains Marian Diamond, of the University of California, Berkeley, by the time we are one or two years old, and it remains constant.
Just as muscles are designed to contract, so the brain’s cells are designed to receive stimuli. And just as regular exercise makes muscles strong, so regular stimulation keeps the brain healthy. “The brain thrives on stimulation,” says Diamond, “and it dies without it. Use it or lose it.,’
Diamond tested this thesis by placing 10 old rats in a cage containing toys. In this enriched environment, and given tender, loving care, the rats lived to 900 days old; the normal life span is around 700 days.
When Diamond examined their brains, she discovered cortical thickening and growth of dendrites equivalent to that of a much younger animal.
Examination of human brains obtained at autopsies, carried out by Paul Coleman, professor of anatomy at the University of Rochester, revealed that brains from normally healthy people, ranging in age from 68 to 92 years, had actually grown longer and more extensive dendritic trees than the brains of middle-aged adults.
But even if our brains can stay healthy far beyond our current life spans, they could nonetheless be causing other systems in our bodies to deteriorate. They may, for instance, influence our hormones detrimentally.
To take one example: In 1969, Donner Denckla, formerly with the National Institutes of Health, discovered that oxygen consumption goes down with age. Trying to find what controlled this process, Denckla removed the hormone-producing glands from rats and discovered that the pituitary secretes a “decreasing-oxygen-consumption hormone,” which he calls DECO. When Denckla removed the pituitary gland from rats, he found their youthful functions were restored, and their life spans increased.
Is DECO a “death hormone”? Perhaps, says Denckla. But the pituitary does not decide when to release DECO all by itself. “Look at it this way,” he says. “The carpenter is the man who has the hammer in his hand to drive the nail. The pituitary is the hammer, but it sure isn’t the carpenter. Where the carpenter is, I wish I knew. It’s probably in the brain.
But if the brain is controlling the endocrine, or hormone-producing, system, the endocrine glands, in turn, affect the immune system. And obviously, to reach a vigorous old age, we need our immunities in order to stay healthy and resist any bodily erosion from disease. Now, it appears, there may be an immunological fountain of youth in hormones secreted by the thymus, a gland once considered a useless vestige of evolution. “Whether we grow old gracefully immunologically depends in great part on whether the thymus gland is functioning properly,” says Allan Goldstein, chairman of the department of biochemistry at the George Washington University School of Medicine and Health Sciences.
EARLY FIFTIES: The clock speeds up. Wrinkles become more visible as skin begins to loosen and sag. Eyes begin to rail at close range; nearsighted people may attain “normal” vision as the two effects cancel out. Many women’s glands stop secreting the sex hormones; they pass through menopause and out of the reproductive phase of their lives. The pancreas produces less of two chemicals, trypsin and insulin; therefore diabetes becomes more likely. Thumbnails grow more slowly. The sense of taste becomes less acute.
The fountain of youth may lie in hormones secreted by the thymus.
The role of the thymus as immunological czar began to emerge in the early 1960s when Goldstein, then a postdoctoral fellow, and his mentor, the late biochemist Abraham White, discovered a family of thymic hormones that they named thymosins. Since then, Goldstein has discovered that thymosins restore immune systems of old animals and may do the same for humans.
The thymus gland and its hormones control the production and function of three different types of white blood cells, or lymphocytes, known as T cells. Some T cells produce lymphokines, the immune system’s natural drugs, such as the cancer fighter gamma interferon. “T-helper cells” help to produce antibodies. The third type, “T-suppresser cells,” regulate the immune system and keep it from attacking the body’s own tissues.
Most recently, Goldstein and his research team have learned that some thymosins also stimulate hormones in the brain, such as ACTH, the hormone that stimulates the production of cortisone, which helps relieve rheumatoid arthritis, and beta endorphin, the “feel good” hormone that is released during jogging, sex and childbirth.
One reason our thymus-controlled immune systems become less effective as we grow older is that the thymus itself begins to age. At birth, it’s about the size of a walnut. Around puberty it begins to shrink, and by old age it may be less than one-tenth its original size. The gland continues to function throughout our lives but with decreasing efficiency after we reach 40. The highest levels of thymosins in the blood occur from birth through five years of age, says Goldstein.
William Ershler, of the University of Vermont School of Medicine, has made test tube studies of the effects of thymosins on human lymphocytes. He cultured white blood cells from college students and from people over 65, all of whom had received tetanus shots, and then stimulated the cells with different dosages of thymosins. With thymosins, Ershler reports, old people’s white blood cells can be stimulated to produce the same amounts of tetanus antibodies as the lymphocytes of young people. He is now testing the effect of thymosins on white blood cells from young and old people who have received flu vaccine. The preliminary data suggest that thymosins improve the vaccine’s effectiveness, reports Ershler, who plans to give them along with flu shots to healthy old people next year.
LATE FIFTIES: Rapid changes. At 55 as muscles and other tissues start to decrease in weight, and more body fat may accumulate. But the production of man’s speaking voice may rise from C to E-flat as vocal cords stiffen and vibrate at a higher frequency. Billions of neurons in the brain become inactive, yet only a slight memory loss will be noticed In an average, healthy adult.
“Ageing is not an accumulation of insults, as some people believe.
Thymosins may also help in the treatment of cancer. Recently, lung cancer patients who were given thymosins in conjunction with radiation were disease-free for longer periods of time before relapse than patients without extra thymosins. The results were sufficiently encouraging for the National Cancer Institute to set up several studies to confirm the finding.
Thymosin supplements also seem to help pre-AIDS patients, those at the highest risk of acquired immune deficiency syndrome. “In some of the patients, we’ve seen significant reconstitutions of some of their immune responses,” says Allan Goldstein. He adds that gerontologists are particularly interested in this discovery because “the suppression of the immune system that is due to the infectious agent in AIDS results in many of the same phenomena that are seen with ageing in terms of increased susceptibility to infections and certain types of malignancies. Even though ageing isn’t caused by a virus, through an understanding of what is happening in AIDS, we’ll be able to learn a great deal about the immune system which would apply to ageing as well as to other disease processes.”
Goldstein has developed a test for measuring thymosin levels in the blood that may become a routine part of physical examinations in the near future. He hopes that thymosins in healthy adults will be monitored so that doctors will know when to begin replacement therapy. “In the future,” he says, “I think that thymosins may play a very important role in preventive medicine.”
Another bodily substance that seems to decline with age is a steroid, DHEA (dehydroandrosterone). According to Robert N. Butler, former director of the National Institute on Ageing, DHEA’s function is unknown, but experimental doses prevented tumours in mice that had been bred specifically to develop breast cancer. It also seems to lower cholesterol levels and reduce obesity.
While some scientists are hot on the trail of involuntary body systems that affect ageing, others are studying what we do wilfully to ourselves that eventually wears us down. Roy Walford has proposed we could live to 120 if, early on, we began restricting the amount of food we eat.
The food-restriction principle, first discovered by Clyde McCay at Cornell University in the 1920s and ’30s, has been repeatedly confirmed by researchers in many laboratories. At UCLA, Walford and Richard Weindruch have taken mice and, after weaning, fed them a diet relatively low in calories but supplemented with vitamins and minerals. Mice that are undernourished but not malnourished live from 25 percent to nearly 100 percent longer. It’s also possible, reports Walford, to begin caloric restriction in mid–adulthood and still extend the life span, but the restriction must be gradual.
Walford has also extended the lives of Argentinian annual fish, which normally live only a year. By restricting a fish’s diet during the first half of its life and lowering the water temperature nine degrees thereafter, Walford and Liu kept the fish alive for three years.
Other scientists, rather than concentrating on how much food we eat, have tried to discover the relationship between diet and ageing. The most dramatic study comes from the laboratory of Paul Segall and Paola Timiras at the University of California, Berkeley. By placing three week old female rats on a diet deficient in tryptophan, the amino acid essential for growth, Segall and Timiras doubled some of the animals’ life spans from the normal 701 days to 1,527 days, and extended the rats’ reproductive life from the normal 15 months to 33 months. Segall reports that a 33-month-old rat gave birth to perfectly formed live pups. This would be roughly equivalent to an 80-year-old woman having a baby.
Taking Drastic Measures
Tryptophan reduction is a drastic measure, however: It kills off half the test animals within a year. Those that survive have convulsions, tremors and extreme nervousness. Nevertheless, among animals that can stand it, the more severe the tryptophan deprivation, the longer the animal survived. “This is quite the opposite of what’s expected,” says Se-gall. “What’s expected is that the worse you treat an animal, the shorter the time it’s going to live. But this isn’t what we find. The semi-starved, growth-stunted animals are the ones in which the ageing process is slowing down. This makes me think that ageing may not be an accumulation of insults, as some people believe.”
Because of its severe side effects, says Segall, “I don’t see us refining the tryptophan-deprival method to use on humans in any way. It’s a strategy for getting at the ageing process, and I believe you have to use very drastic measures in order to see the anti-ageing effect most clearly.”
All of our accumulating knowledge about ageing now suggests a mosaic of causes. Some seem genetic. For instance, children who grow and mature slowly or who come from long-lived families seem to live longer than the rest of us. “But what you lack in genes, you can make up for in life-style,” says forensic anthropologist David Wolf, of the state medical examiner’s office in Frankfort, Kentucky.
Environment, life-style, stress and diet all affect ageing. Seventh-Day Adventists, for example, are largely vegetarians, and they live seven years longer on average than a comparable non-Adventist population.
How long you last may also depend on where you live. In certain parts of the world-the Caucasus Mountains in the Soviet Republic of Georgia, Kashmir and Vilcabamba, a village high in the Andes of Ecuador-people seem to maintain health and vigour into advanced old age. It’s hard to say just how old these people really are. Records to support claims of 135 are non-existent, and experts now believe that the oldest are around 110.
As recently as the middle of the last century, half of all Americans died by the age of 40.
Within the United States, there are more than 3,000 counties in which consistent longevity has been identified. In 82 of them, the age-adjusted death rate from natural causes for white males aged 35 to 74 is under 9.6 per 1,000 per year. In 21 counties whose inhabitants are notably short-lived, the death rate is above 20 per 1,000.
In most counties, life spans are growing. In the United States, a white female child born today can expect to live to almost 80. According to the Bureau of the Census, there are now more than 32,000 Americans aged 100 and up, almost 300 percent more than there were in 1960.
And not only in the United States. The proportion of elderly people to young is increasing everywhere, creating what physician David Hamburg, president of the Carnegie Corporation, calls an “evolutionary novelty.” Even as late as the mid-nineteenth century, half of the population died by the age of 40. Half of all the people on Earth who ever lived past the age of 65 are alive today.
Some observers argue that postponing death would create an intolerable social crisis. Retirement would come later, benefits would have to be paid longer, and fewer jobs would open up for younger workers.
Gerontologists, however, insist we can postpone death longer and longer-beginning almost immediately-if the appropriate studies are funded.
This is a familiar cry among scientists, many of whom grouse that their speciality is unfairly impoverished. Still, so many researchers seem on the verge of untangling the secrets of ageing that a commitment to their work, similar to the commitment we gave to space in the 1960s, might produce an unprecedented evolutionary breakthrough for the human species. We might even enter the twenty-first century as the first generation ever to enjoy lifelong health.
And someday, we might even beat death.
SIXTIES AND SEVENTIES: The clock slows down. At 60, a person is three-quarters of an inch shorter than in youth; at 70, a full inch. # At 60, a man has half the strength. In his biceps as at age 25. # The capacity of the lungs has decreased by half. # At 70, nose, ears and earlobes are longer by one-quarter to one-half an inch. # Only 36 percent of the taste buds remain active. On average, white males live to 71.4, white females to 78.7. Past 75, blacks’ life expectancy is greater than whites’
- Research On Ageing
Although it appears that the human life span has a fixed maximum of about 110 to 115 years-and
has had for the past 1,000 centuries-life expectancy has increased. In the United States, it has grown from 70.8 years in 1970 to 74.5 years for the total population in 1982. Significantly, the quality of life in old age has improved as well. With intervention in the form of diet, exercise and weight control, people have not only been living longer but staying healthier.
- · Could science learn to turn the ageing process off? Perhaps. Biologist Eduardo Zeigler of Stanford has found that ageing plants can be made young again. Yellowing lower leaves, it was found, will return to a healthy green if the tops of the plants are cut off. To be sure, this practice does not readily translate into a treatment for ageing humans. However, scientists are encouraged that, at least among some living things, lost youth seems to be retrievable. Indeed, further research has shown that the use of certain hormones may also help plants combat the ageing process.
- · Psychiatric disorders are more likely to occur among young adults than among people over 65, or so concludes a preliminary report by the National Institute of Mental Health. While the elderly will show a greater incidence of general intellectual malfunction, most serious psychiatric illnesses-such as depression disorders and antisocial personality will occur, if at all, among the young.
- The brain, it seems, can get better as it gets older. A study at the University of Rochester shows that brain cells continue to grow and develop well into old age. The researchers say that, at some point, the cells may begin to degenerate faster than they grow; but of all the brains they studied, one of which was 92 years old, none showed evidence of such deterioration.
Stephanie Bernardo and Kenneth Jon Rose
HOW EXPERTS COPE WITH AGEING
Do the researchers who explore the mechanisms of ageing do anything to counter ageing in their own bodies?
“I don’t,” admits Dr. William Ershler, of the University of Vermont, “though I’ve thought about it as my hair turns a little grey.” His work concerns the thymus gland, which controls our disease-fighting immune system. He believes that someday many people will routinely take the kind of thymic hormones, or thymosins, he now studies. “They will be taken possibly as a prophylaxis for the immune deficiency of ageing or as a treatment for immune-deficient old people.” At present, however, all such studies are closely regulated by the Food and Drug Administration, he notes, and “investigators aren’t meant to take a little on the side.”
Were he to do anything, Ershler says, he’d settle for taking zinc. “Zinc has been shown to be very much involved with the immune response,” he notes. “Zinc levels do go down when you’re ageing, and they correlate well with immune deficiency in ageing-at least in mice. But I don’t know if taking zinc in the diet is satisfactory to replenish levels in the tissues. There might be some mechanisms that control the zinc levels that we just don’t understand yet.”
Thymosin researcher Allan Goldstein, who at 46 ruefully describes himself as an “ageing biochemist,” monitors his own thymosin levels and finds they are in decline. “I don’t smoke, I exercise and jog, take multivitamins and minerals, including vitamin C, enjoy my family and work [emotional deprivation is a severe stress for the immune system-yet I’m ageing like everyone else,” he admits. He, too, believes that in the near future, thymosin supplements will be taken as casually as vitamins to boost the immune system, and he plans to add them to his regimen. By stimulating the production of hormones such as beta endorphin and ACTH, he says, “thymosins may have an effect on the ageing of the brain.” In the meantime, he’s becoming “more serious about the aspects of his work that affect ageing.
A Weekly Fast
Roy Walford of UCLA is even more active. He is well into the third year of a self-imposed calorie-restriction program that will gradually reduce his weight by around 15 percent through undernourishment (but not malnourishment). Walford fasts one or two days a week. “The rest of the time I don’t eat that much less-to lose weight over five or six years doesn’t take that much less than you usually eat.” In moderate doses, he also takes antioxidants, such as vitamin E. These help rid the body of oxidising agents that can damage tissues in the ageing process.
If undernourishment is not your style, you may prefer Paul Segall’s approach. A physiologist from the University of California, Berkeley, he explains: “I’m going to be frozen when I die. A team of people will take my body and perfume it with agents that protect it against the cold and put me in a capsule filled with liquid nitrogen.”
Segall says his work with tryptophan deprivation in mice to extend reproductive life is only one aspect of his involvement with the seven life-extension sciences: interventive gerontology (altering the ageing process), suspended animation, transplantation, artificial organs, resuscitation, regeneration and genetic reconstruction, or cloning. “Raising public consciousness about the breakthroughs imminent in these seven areas will do more than individual precautions to enhance the human life span. We’re maybe not even a decade away from a lot of this,” he says. “All that’s needed is R&D