MORTALITY

Genes are the ultimate time travelers. They transcend the bounds of time by hitching a ride in sexually reproducing species such as humans, but then discard the human body later in life as if it was a used car that had passed its warranty period. Once immortality became a fundamental property of deoxyribonucleic acid (DNA), at some time in the distant history of life on earth, the carriers of these genetic codebooks for constructing living organisms, including humans and other sexually reproducing species, became disposable. The timing with which death occurs—both for individuals, as measured by their lifespan, and collectively for populations, as measured by life expectancy—defines the concept of mortality.

Although it is not possible to know with certainty when any single individual will die, it is known with surprising accuracy when death occurs for members of a population when viewed as a group. In humans and a large number of other species, scientists have demonstrated that the risk of death is highest just after birth, declines to its lowest point near the time of sexual maturation (puberty), and then increases exponentially until extreme old age.

Why is this age pattern of death so common among sexually reproducing species? Early in life, death rates are high because newborns are subject to mortality risks from infectious and parasitic diseases, predation, and congenital malformations. Puberty is the time of lowest mortality because, from an evolutionary perspective, this is the moment at which the investment in the next generation has reached its maximum. This implies that the body design of humans and other living things are constructed with the ultimate goal of reproduction in mind (e.g., the passage of genes from one generation to the next), so this time of life is the most highly protected of all times in the life span. Following puberty, the risk of death from intrinsic (aging-related) causes increases exponentially because of a combination of wear and tear to the physical components of the body; accumulated damage to DNA, cells, tissues, and organs, highly efficient but nevertheless imperfect maintenance and repair mechanisms; and because of the presence of lethal inherited genes that "leak" into the gene pool of every generation.

Scientists have demonstrated that the rate of increase in the death rate following puberty is often calibrated to the length of each species' reproductive window, which is the average duration of time that elapses between puberty and menopause. In other words, animals like mice that experience puberty within weeks after birth tend to age much more rapidly and live considerably shorter lives than sea turtles, which do not experience puberty until about fifty years after birth. As a result of these differences in the rate of aging across species, one day in the life of a human is, in terms of percentage of life span, equivalent to about one week in the life of a dog and one month in the life of a mouse.

Death is an event that can and does happen at every conceivable age in a genetically diverse population. The death rate (also referred to as the mortality rate) for a population may be calculated in its simplest form as the number of deaths that occur in a given year divided by the population at risk of death, the product of which is then multiplied by a standard number (such as one thousand) to give the statistic more intuitive meaning. For example, in the United States in 1995 there were 2.3 million deaths and 262.8 million people alive in the middle of that year. This means that the crude death rate for the United States in 1995 was 8.8 deaths per thousand people [(2.3 / 262.8) × 1,000 = 8.8]. Death rates may also be calculated for people of various age groups or by single-year-of-age, and are often used to estimate the life expectancy of a population.

The various ages at which death occurs provides useful information about the longevity attributes of a population. For example, if one were to imagine a hypothetical group or cohort of one hundred thousand babies born in any given calendar year, and one applied to those babies throughout their lives the death rates that prevailed at every age in that year, it would be possible to plot on a graph the hypothetical ages at which all of the babies would have died. This is known as the distribution of death for a population. Although the distribution of death in 1900 was characterized by high mortality early in life, for those who lived beyond the perilous early years, the modal age at death for females was about 73 years of age (see Figure 1). A comparable distribution of death was observed for males in that year.

The opposite of the distribution of death is a plot of the number of people that are expected to survive from one year to the next. This is known as a survival curve. The survival curve is another useful tool for examining age patterns of death and survival in a population because it provides summary statistics that are easy to interpret and understand. For example, from the survival curve for U.S. females born in 1900 it may be determined that, based on the death rates that prevailed in that year, 58 percent would have been expected to survive to the age of fifty (see Figure 2). By contrast, an estimated 95 percent of the female babies born in the United States in the year 2000 are expected to survive to at least their fiftieth birthday. This demonstrates the dramatic improvements in survival that occurred at younger ages during the twentieth century. In 1900 in the United States the survival curve for females illustrates that the median age at death (the age at which 50 percent of the babies born in that year will still be alive) was fifty-eight years of age. By the year 2000 the median age at death for females in the United States was eighty-three years. As shown in Figure 2, based on death rates observed in the U.S. in 2000, an estimated 86 percent of all the female babies born will survive at least to their sixty-fifth birthday—a dramatic improvement that occurred during the twentieth century. Both curves provide actuaries, demographers, and other scientists with valuable information that can be used to compare the same population across time, or different populations during the same time period.

The Gompertz Equation and its relationship to mortality

In 1825 an English actuary by the name of Benjamin Gompertz made an important discovery. Gompertz's job as an actuary for an insurance company was to calculate the risk of death for people of different ages in order to determine how much to charge for life insurance. (The exact same kinds of calculations are made by actuaries today.) Using data from various parts of England, where he lived, Gompertz discovered that the risk of death increased in a predictable fashion with age. His calculations led him to conclude that the death rate doubled about every ten years between the ages of twenty and sixty, which was the primary age range for people purchasing insurance annuities at that time. The mathematical formula Gompertz used to predict this exponential rise in mortality after age twenty has become known colloquially as the Gompertz equation, and it has remained an integral part of mortality computations conducted by actuaries and demographers ever since the early nineteenth century.

What made Gompertz's discovery so interesting was not just the fact that he devised a formula that accurately portrayed the dying-out process of humans, but that he and others believed that the same formula could be used to characterize death rates for other species. In fact, for more than a hundred years following Gompertz's discovery, numerous investigators from a wide range of scientific disciplines speculated that the Gompertz formula described a fundamental principle of death for all living things, a principle that became known as the Universal Law of Mortality. Recently, scientists have used death statistics for such species as humans, mice, and dogs to demonstrate that there is evidence to support the idea that age patterns of death occur in a consistent way across species, despite the fact that there is a wide variation in the observed lifespans of different species. In other words, there is scientific evidence to suggest that Gompertz was right—there appears to be a nearly universal age pattern to the dying out of living things.

The biology of life span

Why do people and other living things endure as long as they do? Why aren't we immortal? The answer to the most basic question of why we age is still an unsolved problem in biology, as the late famous biologist Sir Peter Medawar said in 1951. However, scientists are quickly closing in on at least some of the possible reasons why aging occurs. One of the most prominent theories of aging today is known as the free-radical hypothesis. During the process of metabolizing food and water and operating the machinery of life in a toxic world, damaging substances known as free radicals are generated. Although the human body has a highly efficient mechanism to protect itself from these damaging substances, it is not perfect. It is this lack of perfection that leads to accumulated damage to the DNA contained within the nucleus and the mitochondria (energy factories) of most cells. The level of damage moves up the scale of biological organization from DNA to cells, tissues, organs, organ systems, and ultimately to the whole organism—contributing to a degradation in the functioning of biological systems and an increased susceptibility to the diseases now associated with aging. Even though the damage that occurs to DNA is itself repaired with near perfection, it is the lack of perfection that is the basis for the free-radical hypothesis of aging.

There are a number of other prominent theories about the mechanisms of aging. Among them are the wear-and-tear theories and the discovery of an attribute of nuclear DNA known as the telomere. If the human body is viewed as a living machine with pulleys, pumps, levers, and hinges, much like that of a man-made mechanical device, it is evident that such machines cannot be operated indefinitely because of wear and tear. There are changes that occur in most human biological systems with the passage of time, including the loss of bone and muscle mass, increased brittleness of the circulatory system, and a degradation of the immune and reproductive systems.

Telomeres are the end caps of nuclear DNA, and they are known to shorten in length with each cell division. When they become short enough, the cell experiences a phenomenon known as programmed cell death, or apoptosis. An enzyme referred to as telomerase is known to be present in larger quantities in cells that are protected from aging, such as eggs, sperm, and stem cells, but there is no evidence so far to suggest that adding telomerase to other cells in the body would extend length of life. Although some scientists believe that this is one of the major biological mechanisms that contributes to aging, most people tend to die well before telomere shortening poses a serious problem for the whole organism.

Mortality in the twentieth and twenty-first centuries

During the twentieth century, humanity witnessed the most dramatic declines in death rates and increases in life expectancy at birth than at any other time in history. Based on prevailing death rates in 1900, male and female babies born at that time were expected to live to 46.4 and 49.0 years, respectively. Now that the twentieth century has passed, it is known that babies born in the United States in 1900 fared a little better than predicted at the time because of unanticipated declines in death rates that occurred at every age throughout the century. There were three main forces that led to these declines in mortality. The first, which occurred early in the century, was a rapid decline in the risk of death among infants and children. The combination of improved sanitation, refrigeration, the more widespread use and distribution of clean drinking water, and the development of controlled indoor living and working environments led to rapid declines in the risk of waterborne and airborne infectious and parasitic diseases (IPDs). Infants and children benefitted the most from these developments because their immature immune systems placed them at a higher risk of death from IPDs. Examples of some of the IPDs that waned early in the twentieth century include diphtheria, tuberculosis, smallpox, and cholera. The second force that led to declining death rates was the more widespread use of hospitals for childbirth, which contributed to declines in both maternal and infant mortality. The third factor was the introduction of antibiotics in the middle of the century, which has saved people of all ages from a wide range of bacterial infectious diseases. The fourth factor, which led to declining death rates at middle and older ages in the latter third of the twentieth century, occurred as a combination of improved lifestyles, advances in surgical procedures, the development of pharmaceuticals, and a host of other advances in the biomedical sciences. In this case, death rates from such chronic degenerative diseases as heart disease and some cancers were observed to have declined during this period. As evidence for the magnitude of the changes in mortality that occurred throughout the twentieth century, consider the fact that life expectancy at birth rose by thirty years during this time, which was an increase of magnitude and speed that exceeded that observed during the previous 100,000 years.

There is considerable speculation among scientists about the future of human longevity. Some believe that medical progress will continue into the future at a pace that is even faster than the remarkable gains made in recent decades. Such advances will certainly include new surgical procedures and pharmaceuticals to combat the consequences of aging-related diseases, but advances are also expected in genetic engineering and in research involving embryonic stem cells. Even more speculative, but certainly within the realm of possibility, are longevity gains that could arise from efforts to combat the aging process itself. Although there is reason to be optimistic that death rates will continue to decline in the future, some scientists have demonstrated that the rise in life expectancy will probably be much slower in the twenty-first century than it was during the twentieth century. This is because it is far more difficult to add decades to the lives of people who have already lived seventy years or more than it was, early in the twentieth century, to add decades to the lives of children saved from dying of infectious diseases. However, under any condition, humanity is embarking on a fascinating new journey into the science of aging that will undoubtedly change modern notions about aging and death.

S. Jay Olshansky

See also Life Expectancy; Life Span Extension; Longevity: Reproduction; Longevity: Selection; Longevity: Social Aspects; Theories of Biological Aging.

BIBLIOGRAPHY

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