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Item Number: LIT-004
PREFACE by Arthur K. Balin M.D., Ph.D., F.A.C.P.
Although functional decline appears to be an inevitable and inescapable consequence of aging, there are often considerable differences between individuals with respect to the rate and extent of this decline. Individuals may be young or old in relation to their number of years. As a result, age-related disease or age-related death may occur at different chronological ages. It follows that the true or practically relevant age of an individual is not adequately defined by the time that has elapsed since birth, but by a figure reflecting the individual's progressive inability to respond adaptively to an environmental stress that leads to a decreased viability and increased vulnerability to death. The degree of age-related vulnerability is defined as "biological age".
There has been a great surge of interest in techniques or treatments that might delay the process of human aging. Transferring information, obtained in the basic research laboratory or from studies with animals, to humans is hampered by the time it takes to ascertain whether a specific intervention will extend the mean and maximum human life span. Aging research will be markedly enhanced by techniques that measure the biologic age of an individual because these tests could be used to estimate the effectiveness of therapeutic interventions designed to retard the aging process and extend the length of healthy, productive life. In this volume we review scientific studies that have measured various parameters that change with chronologic age. Our objective is to explore these parameters and follow longitudinally those which will give the highest likelihood of reflecting biological age.

The molecular mechanisms of biologic aging have been under active investigation by a small number of investigators over the last 40years, but a substantial increase in the quantity and quality of basic aging studies occurred in the mid 1970s, concomitant with the formation of the National Institute on Aging. Development of useful model systems to study aging, along with the advent of the revolution in molecular biology, is likely to greatly accelerate the rate of aging research and increase the likelihood that significant advances will be made in the foreseeable future. We already have the technology to determine why we age. It is only a matter of committing sufficient resources to this problem. Whether we will be able to modify the rate of aging in humans depends on the mechanisms that are responsible for the aging process. Therefore, it is possible that we will discover why we age, and perhaps we will then learn that there is nothing we can do to modify the process.
However, there are a number of clues that have developed that suggest that it might be possible to influence or modify the aging process in whole or in part. Studies have shown that it is possible to alter the basic rate of aging in a number of animal systems. In cold-blooded animals, such as the housefly, cooler temperatures and reduced activity will slow the rate of aging and extend the maximum life span of the longest-lived survivor by 400%. In warm-blooded animals, such as the mouse and the rat, caloric restriction will extend the life span of the longest lived survivor by 200%. Studies have shown, in these animal systems, that these manipulations also retard the appearance of many of the age-related diseases such as diabetes and cancer.

One of the problems with using animal systems to study the basic causes of aging is that many of the effects of a specific intervention or manipulation may be unrecognized when death is the end point of the study. Disease and disordered metabolism are difficult to diagnose in experimental animals because the base of knowledge about diseases in different animal species, the number of veterinarians and the intrinsic difficulty in early detection of disease in animals, and the quantity and quality of veterinary autopsies are inferior to what is available in human medicine. Knowledge of disease and the ability to diagnose early perturbations in the human body makes using the human system particularly appropriate when elucidating the basic mechanisms of human aging. There have been a number of treatments postulated, based on research that already exists, that propose modifying the aging process in humans in whole or in part. Many more are likely to come in future years as a result of the increasing interest and active research being done.

How are we going to tell whether any specific treatment can retard the aging process? At present, the
only reliable way to do this would be to give a group of people the treatment and wait 40 or 50 or 60
years to see whether the treatment worked. Multiple studies would need to be done for every proposed treatment. This will take many lifetimes and enormous expense. In order to provide short cuts to this procedure, we wish to be able to measure the rate of aging in an individual. If we could reliably measure how old a person's body is, then we could give them any specific treatment and measure their biologic age again in a few years and be able to rapidly tell whether a specific intervention was useful in retarding the rate of aging.
A number of individuals have been attempting to develop ways to measure the rate of aging in people. Many of them have given this problem serious consideration for many years and have developed approaches that they believe will be useful. A large proportion of these individuals provide their thoughts and approaches to this problem in this volume.

When a test or battery of tests is developed to determine a human's biologic age, the initial validation of the predictive power of the test must be made by following a group of people serially for sufficient years until they have died and the reliability of the parameters chosen can be ascertained. It would be very discouraging to set up a large study, measure a number of parameters in people for 50 or 60 years, and then analyze the data and learn that no measured parameter predicted biologic age. To try to prevent this outcome, it is necessary to measure as many of the most likely predictive factors as possible. For that reason, it is particularly important to have the thoughts of virtually every investigator that has considered the problem collected in one volume. This handbook should provide the basis on which any investigator trying to set up a study to measure biologic age can draw upon existing expertise. This work will stand as a landmark in the development of our ability to measure human biologic age and therefore to ascertain what interventions can retard the aging process in humans.
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