Why We Get Sick (20 page)

Blood levels of uric acid, another antioxidant, are also correlated closely with a species’ life span. We humans have lost the ability, possessed by most other mammals, to break down uric acid. Because uric acid crystals precipitate in the joint fluid and cause gout, this loss is often cited in medical books as a deficiency in human biochemistry, but, as noted in this extract from a biochemistry text, it may also be an advantage that facilitates our long life:

The flaming painful gouty toe is a cost of a gene that may have been selected because it helps to delay senescence. This gene has effects that are the opposite of those already described, in that the gene gives benefits late in life by slowing aging while exacting its costs throughout adult life. It would be most interesting to see if aging is slower in people with gout.

The levels of an enzyme that repairs abnormal DNA are also higher in longer-lived species. This demonstrates that damage to DNA is a force of selection, and, as with SOD and uric acid, it also demonstrates that nature has found a solution to the problem. If one
sees natural selection as a weak force, one sees free radicals and DNA damage as causes of senescence. Appreciation of the strength of natural selection, however, makes one much more inclined to expect that damage from oxygen radicals and defective DNA is limited by evolved mechanisms that are as effective as they need to be to maximize reproductive success.

As Austad points out, the mechanisms of senescence are likely to differ from species to species. Rats and mice, the subjects of most senescence research, are distant from humans, not only phylogenetically but also in their patterns of senescence. Austad therefore proposed extensive cross-species studies of senescence to uncover common patterns. He began his research on an island off the coast of Georgia where opossums had been living without predators for several thousand years and predicted that they would have evolved longer life spans. The field work—catching opossums on both the island and the mainland and determining their ages—took several years. (The task was much easier with the island opossums, because they sleep on the ground in plain view, having lost the defense, essential on the mainland, of hiding all day in deep burrows.) The results of the study? Not only do the island opossums live longer than their landlocked distant cousins, they also age more slowly on a variety of indicators. The cost of these changes, however, is smaller litters at all ages and delayed age at first reproduction. It is clear that the rate of senescence, like other life-history characteristics, is shaped by natural selection.

B
ack to humans. Boys born in the United States in 1985 are expected to live seven years less, on average, than girls, and comparable differences have been found in other countries and in earlier times. Why do women have this advantage over men? The most important evidence for why males age sooner in so many species comes from a cross-species comparison. Males that must compete for mates have shorter lives than females. Part of the increased mortality results from males fighting over females, but even males living alone in cages die sooner than females.

Why are males the vulnerable sex? Male reproductive success is so dependent on competitive ability that male physiology is devoted more to this competition and proportionately less to preservation of the body. Their game of life is played for higher stakes. If unusually fit males can sire large numbers of offspring while mediocre males usually have none, heavy sacrifices must be made in the effort to reach high fitness. Among the processes sacrificed may be those that contribute to longevity.

R
esearch on senescence seems to be discovering the value of an evolutionary point of view. Gerontologists are realizing that the mechanisms that cause senescence may not be mistakes but compromises carefully wrought by natural selection. An evolutionary view suggests that more than a few genes are involved in senescence and that some of them have functions crucial to life. These genes express their various effects in a seemingly coordinated cluster of escalating signs, because any gene whose deleterious effects occur earlier than those of other genes will be selected against the most strongly. Selection will act on it and other genes to delay its effects until they are in synchrony with those of other genes that cause senescence. This process explains the one-hoss shay effect, the concordance of many signs of senescence even though there is no internal clock that coordinates senescence.

This view discourages the hopes of that lady on the plane, the hope that senescence is a disease that may someday be cured. Hopeful talk about a life-extending research breakthrough is just hopeful talk. What gerontological research does offer, and what justifies considerable investment in studying the mechanisms of senescence, is the likelihood that many diseases of senescence can be postponed or prevented so we can live more fully and vigorously throughout adult life. Despite our pessimism about substantially extending the life span, we concede that the history of science is full of confident theoreticians proving something impossible just a few years before it is accomplished. And we are well aware that natural selection has greatly increased our life span in just a few million years. So we ask
not that gerontologists give up their efforts to extend the life span, only that they conduct them in the light of evolution.

We should also note that pessimistic assessments of what science can accomplish often have substantial utility. They provide what philosopher E. T. Whittaker called
postulates of impotence
. Because of such pessimism, engineers no longer try to design perpetual-motion machines and chemists no longer try to turn lead into gold. If gerontologists stop trying to find the fountain of youth in some single, controllable cause of senescence, their efforts may prove more fruitful for human well-being.

The clinician has more immediate concerns. The proportion of people over the age of eighty-five is growing six times faster than the population as a whole. In just the past three decades, the average life expectancy in the United States has gone from 69.7 to 75.2 years. More than a quarter of every health care dollar is now spent on patients in the last year of life, and the need for nursing home beds is expected to quadruple in the next twenty years. Medicine has changed its focus from acute diseases of children and younger adults to chronic diseases of the elderly. Doctors who imagined spending their careers giving antibiotics to stop pneumonia and doing heroic curative surgery now find themselves monitoring high blood pressure, evaluating memory problems, and relieving the symptoms of chronic heart disease. Many of these physicians and their patients still think of senescence as a disease. We expect that knowledge about the evolutionary origins of senescence will have profound effects that are difficult to predict.

This perspective may also change how we see our own lives. Some may find it a consolation to know that senescence is the price we pay for vigor in youth. There is also relief as well as disappointment in knowing that no medical advance is ever likely to extend our lives to any dramatic extent. The search for some pill or exercise or diet that can save us from senescence may be replaced by an appreciation of life as it is, of vigorous function at whatever age. The preoccupation with living forever is likely to be supplanted by a desire to live as fully as possible, while it is possible.

P
hil, the unfortunate television weatherman who lives one day over and over again in the movie
Groundhog
Day, enters a restaurant just as a diner begins to choke on a bite of food. Phil, having observed this scene many times before, calmly steps behind the gasping man, wraps his arms around the man’s upper abdomen, and suddenly squeezes hard. The food is expelled from the diner’s windpipe and he can breathe again, his life saved by Phil and the Heimlich maneuver.

About one person in a hundred thousand chokes to death each year. While this death rate is small compared to that from automobile accidents, choking has been a persistent cause of death not only throughout human evolution but throughout vertebrate evolution because all vertebrates share the same design flaw: our mouth is
below and in front of our nose, but our food-conveying esophagus is behind the air-conveying trachea in our chest, so the tubes must cross in the throat. If food blocks this intersection, air cannot reach our lungs. When we swallow, reflex mechanisms seal off the opening to the trachea so that food does not enter it. Unfortunately, no real-life machinery is perfect. Sometimes the reflex falters and “something goes down the wrong pipe.” For this contingency we have a defense, the choking reflex, a precisely coordinated pattern of muscular contractions and tracheal constriction that creates a burst of exhaled air to forcibly expel misdirected food. If this backup mechanism fails and an obstruction blocking the trachea is not dislodged, we die—unless, that is, Phil or someone like him happens to be nearby.

But why do we need the protective mechanisms of traffic control and a backup choking reflex? It would be so much safer and easier if our air and food pathways were completely separate. What functional reason is there for this crisscross? The answer is simple—none at all. The explanation is historical, not functional. Vertebrates from fish to mammals are all saddled with an intersection of the two passages. Other animal groups, such as insects and mollusks, have the more sensible arrangement of complete separation of respiratory and digestive systems.

Our air-food traffic problem got started by a remote ancestor, a minute wormlike animal that fed on microorganisms strained from the water through a sievelike region just behind the mouth. The animal was too small to need a respiratory system. Passive diffusion of dissolved gases between its innermost parts and the surrounding water easily supplied its respiratory needs. Later, as it evolved a larger size, passive diffusion was ever less adequate, and a respiratory system evolved.

If evolution proceeded by implementing sensible plans, the new respiratory system would have been just that, a new system designed from scratch, but evolution does no sensible planning. It always proceeds by just slightly modifying what it already has. The food sieve at the forward end of the digestive system already exposed a large surface area to a flowing current. With no special modifications, it was already serving as a set of gills by providing a large proportion of the needed gaseous exchanges between internal tissues and environment. Additional respiratory capacity was created by slow modifications of
this food sieve. Rare minor mutations that made it slightly more effective in respiration were gradually accumulated over evolutionary time. Part of our digestive system was thereby coopted to serve a new function—respiration—and there was no way to anticipate that this would later cause great distress in a Pennsylvania restaurant on Groundhog Day. Today, the food-sieving worm stage in our evolution is still found in the closest invertebrate relatives of modern vertebrates, which have combined respiratory and digestive passages, as shown in
Figure 9-1
.

Much later, the evolution of air breathing caused some other evolutionary changes that we now have cause to regret. When part of the respiratory region was modified to form a lung, it branched off the lower side of the esophagus that led to the stomach. Accessory openings for air breathing at the surface of the water evolved, understandably, from the already available olfactory organs (nostrils) on the upper surface of the snout, not on the chin or throat. So the air passage opened above the mouth opening and led into the forward part of the digestive tract. Air then passed back through the mouth and larynx to where the trachea branched off and went through this passage to the lungs. This is the lungfish stage (see
Figure 9-2
).

Subsequent evolution moved the connection from the nostrils back into the throat so that the air passage was as completely separate from the digestive system as it could become without redesigning the structure of the head and throat. Thus a long dual-function passage was gradually shortened until only the crisscross remained, but we and all higher vertebrates are still stuck with it. Vertebrates have the unenviable capacity to be asphyxiated by their food. Darwin pointed out, in 1859, how difficult it is, from a purely functional perspective, to

We are actually worse off than other mammals because traffic control in our throat is further compromised by modifications to
facilitate speech. Did you ever watch a horse drinking? It keeps its mouth in the water and drinks without interrupting its breathing. It can do this because the opening from its nasal region can be precisely lined up with the opening into the trachea. The respiratory passage forms a sort of bridge across the digestive passage, so that when the horse swallows, it can make use of space to the left and right of the bridge. Unfortunately for us, our tracheal opening has slipped further back in the throat, so that the bridge connection can no longer be made. At least not for adults; babies, for the first few months of life, can swallow liquids and breathe simultaneously, like many other mammals. Once they start making the babbling that is the precursor of human speech, however, they can no longer drink like horses. The human capacity for choking represents an ancient maladaptive legacy aggravated by a much later compromise.