Aging and Longevity, Biology of
AGING AND LONGEVITY, BIOLOGY OF
Most strains of mice live an average of 1,000 days; dogs live approximately 5,000 days; and humans, in low mortality countries, live about 29,000 days (around 80 years). The average duration of life of a species and the age-specific rate of increase in the risk of death is calibrated to each species' unique pattern of growth, development, and reproduction. These linkages between longevity and growth and development are the cornerstone of the scientific understanding of the biology of aging and death and the duration of life of humans and other sexually reproducing species. This entry presents a brief discussion of the biology of aging with emphasis on its implications for human longevity.
Causes of Aging
In its simplest form, aging may be thought of as the accumulation of random damage to the building blocks of life–especially to DNA, certain proteins, carbohydrates, and lipids. The damage begins from conception, occurs in a largely random fashion throughout the body, and accumulates with time, eventually exceeding the body's self-repair capabilities. The damage gradually impairs the functioning of cells, tissues, organs, and organ systems, resulting in the increased vulnerability to disease and a rise in the physical, physiological, and psychological manifestations of aging.
There are many agents of damage including, ironically, the life-sustaining processes involved in converting the food we eat and fluids we drink into usable energy. The primary energy generators of cells are the mitochondria. As they perform their usual function, the mitochondria emit oxidizing molecules known as free radicals that exist for only a fraction of a second. Although free radicals contribute to several important biological processes (e.g., cell communication, immune response), they are also a destructive force. Most of the damage caused by these highly reactive molecules is fixed by the body's impressive mechanisms for surveillance, maintenance, and repair. However, unrepaired damage accumulates and causes injury to the mitochondria and other parts of the cell and extracellular environment.
The process of aging makes us ever more susceptible to the common fatal diseases that we tend to associate with growing older, such as the increased risk of heart disease, stroke, and cancer. Even if medical interventions were to eliminate the major remaining killer diseases, the aging process would continue unabated–making the saved population ever more susceptible to a new set of diseases expressed at even later ages. Aging contributes to a wide variety of non-fatal diseases and disorders such as arthritis, loss of vision and hearing, muscle and bone loss, and a reduction in skin elasticity. It should be noted that aging is not a genetically programmed process that plays itself out along a rigid time frame. Instead, aging can be viewed as an inadvertent byproduct of living beyond the biological warranty period for living machines, which in the case of sexually reproducing species means surviving beyond the end of the reproductive life span.
Forecasting Life Expectancy
How much higher can human life expectancy rise? This question has been the subject of debate among actuaries and demographers for centuries; it has taken on a new practical significance in modern times because it affects the future solvency of the age-entitlement programs found in all modern welfare states. There is a wide range of estimates: Their lower bound accords with the view that life expectancy for human populations (males and females combined) is unlikely to exceed the mid to high 80s; others claim that there is no biological reason why life expectancy cannot rise indefinitely in the future. The sections that follow present the basic arguments of the three main schools of thought that have contributed to this debate.
Scientific forecasts of the survival of individuals and populations began with the practical work of actuaries employed by life insurance companies. Benjamin Gompertz (1779–1865), in an article published in 1825, first identified a common age pattern to the dying-out process. The formula developed by Gompertz showed that the force of mortality among humans increases exponentially from about age 20 to 85. Interestingly, Gompertz's formula provides an accurate characterization of the timing of death not just for humans but also for a variety of other species. When the U.S. Social Security program was created in the 1930s, actuaries needed to make forecasts of the annual number of beneficiaries that would draw benefits from the program. They did so by simple extrapolation: If, for example, life expectancy at birth had increased by two years in the previous two decades, it was projected to increase by another two years in the subsequent two decades.
During the next five decades, using this model, the Social Security Administration (SSA) consistently underestimated the speed with which mortality was declining. The SSA actuaries also believed that the average achievable life expectancy was constrained by biological limits to life, and that there was reason to assume that the population of the United States was approaching those limits. This view was supported by the demographic predictions at that time that the rise in life expectancy at birth would soon begin to tail off.
Toward the end of the twentieth century, the opposite problem occurred–the SSA began to over-estimate the rise in life expectancy. The actuaries, as before, chose as the basis for their forecast a relatively narrow time period. In the earlier projection this introduced a conservative bias, but in the 1970s declines in death rates at middle and older ages were exceptionally rapid. Extrapolation of such rapid gains turned out to be unrealistic.
The extrapolation model, with its implication that life expectancy for humans will continue to rise far into the future, is frequently used. In a 2002 study, Jim Oeppen and James Vaupel remark that the historic rise in life expectancy is one of the most regular biological events ever observed, and argue that there is reason to believe this trend will continue throughout the twenty-first century. They project that life expectancy for humans in low mortality populations will rise to 100 years by the year 2060.
The advantages of the extrapolation method are that it is parsimonious, observation-based, and easily adjusted to reflect new developments in population health and aging. Ample evidence in the scientific literature suggests that when used over relatively short time frames, it has been a highly reliable predictor of trends in life expectancy.
Extrapolation also has weaknesses. Much of the rise in life expectancy in the twentieth century came from declining death rates before age 50. Future rises will have to come mainly from declining death rates at middle and older ages–the prospects for which may not be soundly gauged based on what happened in the earlier period. The absence of biological information as an input to projecting mortality is another problematic feature of extrapolation.
Biodemographic Views of Aging
An alternative approach to forecasting mortality draws on insights from the biodemography of aging. Biodemography is an effort to merge the scientific disciplines of biology (including evolutionary biology, genetics, and molecular biology) and demography and actuarial science in order to understand the biological forces that lead to consistent and predictable age patterns of death among sexually reproducing species. Although the intellectual roots of biodemography date back to the nineteenth century with the search for the "law of mortality," it is only in modern times that biodemographic reasoning has been used to inform mortality forecasts.
According to evolutionary theory, there is a fundamental link between the force of natural selection and the timing of reproduction among sexually reproducing species. The timing of death in populations is thought to be calibrated to the timing of genetically fixed programs for development, maturation, and reproduction. Further, the onset and length of the reproductive window (i.e., for females, the time between menarche and menopause) is thought to influence the rate of increase in the death rate from biological causes–a theoretical underpinning of evolutionary theory that has since been empirically demonstrated.
The main forces that influence the death rates of humans at high life-expectancy levels are those associated with the regulation and pathogenesis of intrinsic disease processes; biochemical changes that contribute to senescence; and biodemographic forces that influence the speed with which life expectancy rises.
In their 1996 study, Bruce Carnes, S. Jay Olshansky, and Douglas Grahn reasoned that the demonstrated linkage between the timing of reproduction and senescence could be used to inform and improve forecasts of human life expectancy. If each species has fixed programs for growth and development, there should be relatively fixed age patterns of intrinsic (biologically-caused) mortality: a species-specific "intrinsic mortality signature." This biodemographic perspective yields a practical upper bound on human life expectancy of 88 years for females and 82 years for males (85 years for males and females combined). Exceeding that boundary, according to this argument, would require modifying the biological rate of aging itself–a technological feat that, although theoretically possible in the future, is currently beyond the reach of science.
Extreme Forecasts of Life Expectancy
According to some claims, advances in the biomedical sciences will be so dramatic in the coming decades of the twenty-first century that life expectancies of 150 years or higher may be attained in the lifetimes of people living in 2002. It has even been suggested that it is currently possible to modify the rate of human aging, and that immortality is a realistic goal for the twenty-first century. The suggestion that medical science is on the verge of discovering the secret to the fountain of youth and that humanity is about to extend life dramatically has been made repeatedly throughout history, with each proclamation contradicted by subsequent experience. What has encouraged many people in the early years of the third millennium to be newly optimistic about the prospects of greatly extending average human life expectancy is that scientists now have pieced together important elements of the puzzle of aging. Also, investigators can claim legitimately that they have experimentally increased the duration of life of a variety of organisms. If it is possible to extend the life of experimental animals, the argument goes, then it should also be possible to make humans live longer.
Advances in the biomedical sciences may well continue to postpone death ("manufacture survival time") by treating the primary fatal manifestations of aging, such as cardiovascular diseases and cancer, but no scientific evidence to date suggests that the rate of aging of any animal has yet been modified. Highly optimistic projections of life expectancy have been supported by evidence of a falling risk of death from major diseases of old age and by the apparent effects of substances like the human growth hormone (GH) on some manifestations of aging. (The latter results have been wrongly interpreted by the proponents of extreme forecasts of life expectancy as a reversal of aging. However, the benefits disappear once GH treatment is stopped; there is even some evidence from animal models to suggest that GH has a life-shortening effect.) In short, there is no theoretical or scientific evidence to support the claims of anticipated dramatic increases in human life expectancy based on existing scientific knowledge.
Questions about the biology of aging and the average longevity of populations have always been of great fascination to scientists and the lay public. The ongoing research of gerontologists from a broad range of scientific disciplines has, in the early twenty-first century, produced a more complete understanding of the underlying biological forces that contribute to aging and the duration of life. Moreover, scientists have succeeded in experimentally extending the lifespan of several non-human organisms, leading some to believe it is only a matter of time before the same will be done for humans.
The significant advances that have been made in understanding the biology of aging are rarely incorporated into the assumptions governing estimates of future longevity. This may have the effect of making contemporary demographic forecasts of human life expectancy overly optimistic–that is, unless advances in the biomedical sciences proceed at a faster pace than in recent decades.
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S. Jay Olshansky
Bruce A. Carnes