Physiological Changes

It is evident even from casual observation of physical activities, such as walking, that elderly people exhibit a deterioration of physiological processes. Moreover, the inability of athletes to continue peak performance when they reach their thirties or forties indicates that deterioration begins at a relatively young age and progresses in severity from that point on. Indeed, many studies have confirmed that most physiological processes deteriorate progressively after about thirty years of age, some functions more severely affected than others.

Most of the research on age-associated physiological deterioration has utilized cross-sectional studies; that is, subjects of different ages are studied at a given point in time (e.g., the calendar year 1990). These are called cross-sectional studies because the data are collected from a cross section of the population. Since this study design provides information quickly and relatively inexpensively, it is widely used. However, because of generational factors and selective mortality, the cross-sectional design can yield erroneous information about aging.

An example of how a generational factor may confound an aging study is illustrated by a hypothetical 1970 cross-sectional study of cognitive function in which Americans in the third decade of life were compared with those in the tenth decade. It is critical to note that the average number of years of schooling of Americans has increased markedly during the twentieth century. Therefore, if this study finds cognitive ability of those in the tenth decade of life to be less than in those in the third decade, it may be due to the difference in educational level or to age-associated deterioration or to a combination of both. Such a study will not show to what extent aging per se plays a role in the findings.

Selective mortality refers to the fact that with increasing age, there is a decrease in the fraction of a birth cohort still alive, and that, on average, those with risk factors for common fatal diseases will die at younger ages than the rest of the cohort. Take, for example, a blood substance known to be a risk factor for a fatal disease. If it is lower in the tenth decade than in the seventh decade, it probably results from the fact that most of the cohort with high levels died before reaching the tenth decade, and not because of an age-associated decrease in blood level of this substance.

In summary, in studies with a cross-sectional design, the findings define age differences within a population at a point in time. These differences may or may not be due to aging, and further studies are needed to assess the role of aging.

One approach for this assessment is the use of longitudinal studies in which the same subjects are studied repeatedly over extended periods of time, for example, ten or twenty years. Such studies circumvent some of the problems inherent in cross-sectional studies, but longitudinal studies are costly and time-consuming. Moreover, they require that most subjects participate throughout the lengthy study, and that their environment and lifestyle do not change during the entire study. In addition, the methodology (analytic methods, instrumentation and skills of the technical personnel) used in the physiological measurements must be stable over this prolonged period of time. One can see that it is difficult to meet the many requirements of a longitudinal study.

Another approach has been the use of a combination of cross-sectional and longitudinal study designs. The bottom line is that investigators must be alert to the possibility of confounders when using the cross-sectional design, and thus, they should be open to utilizing various other approaches in their assessment of the changes in physiological processes due to aging.

Diseases that do not occur until, or increase in frequency at, advanced ages are called age-associated diseases. Coronary heart disease, stoke, many types of cancer, osteoporosis, Alzheimer's disease, Parkinson's disease, and osteoarthritis are examples of such diseases commonly found in elderly people. Indeed, age-associated disease underlies much of the physiological deterioration of old age. However, many investigators have chosen to select subjects who are free of discernible disease in what they refer to as the study of "normal aging." Not surprisingly, such studies have shown remarkably little physiological deterioration in those elderly subjects who are free of disease. For example, Edward Lakatta and his colleagues at the National Institute on Aging in Baltimore have found little deterioration of cardiovascular function even at advanced ages in subjects screened for the absence of coronary heart disease by the sensitive thallium stress test. However, it must be emphasized that "normal aging" is atypical, and that age-associated disease is the rule rather than the exception at advanced ages. Moreover, the concepts of evolutionary biology point to age-associated diseases as an integral part of aging.

In 1969, Ewald Busse of Duke University proposed the concept of primary and secondary aging. Primary aging was defined as universal age-changes, including physiological changes, that are not caused by disease or environmental influences. Secondary aging was defined as changes involving interactions between primary aging and environmental influences and disease. This concept is gradually being discarded because of advances in our knowledge of the evolutionary biology of aging and the recognition that most genes do not function in a vacuum; rather, their expression is clearly the result of gene-environment interaction.

In humans as well as in many other species, there is much individual variation in occurrence, magnitude, and rate of progression of deterioration of the physiological systems. John W. Rowe of Mt. Sinai Medical Center in New York City and Robert L. Kahn of the University of Michigan have proposed the concept of "successful aging" to refer to the elderly who exhibit little physiological deterioration. They believe that factors, such as exercise, diet, personal habits and psychosocial influences, play the major role in achieving "successful aging." This focus is unfortunate because it is the interaction between genes and environment that usually plays the major role in physiological functions rather than genes per se or environment per se. Another concern is the implication by Rowe and Kahn that advanced age culminating in death occurs without marked physiological deterioration in those undergoing "successful aging." The facts simply do not support this. Most centenarians exhibit much physiological deterioration, although any of these individuals would have been described in their ninth decade of life as having undergone "successful aging." It is perhaps more appropriate to say that aging occurs slowly in some people, rather than to say they have undergone "successful aging."