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Feature Article - e-Journal of Age Management Medicine - October 2006
Measuring Biological Age vs. Chronological Age in an Age Management Practice

Elliott Small

This article is divided into two sections:

Practical Technology Available to Age Management Practices

There is controversy regarding the measurement of biological age. Yet, the ability to measure a patient's level of aging can provide great benefits to an Age Management Practice. Controversy can be avoided by shifting some of the focus to functional age rather than biological age. Unlike some biochemical tests, whose relevance is often based on theory, it is more evident that changes in memory and other cognitive functions, lung function, reaction time, hearing, touch, vision, muscle movement speed, etc. are part of the aging process. What is universally recognized as aging, apart from appearance, is the loss of ability to function. Status of life functions is the result of the underlying biochemical status. Measurement of life functions is, in effect, a shortcut to perceive the effects of the biochemical processes that are still more difficult to understand and measure directly. With this focus, it is possible to achieve these benefits in an Age Management Practice:

MEASURE ABILITIES NEEDED FOR A SATISFYING LIFE: Patients come to an Age Management Practice because they want to retain or recover the functions required to enjoy life. Tests that focus on familiar life functions can more fully capture the interest of the patient.

TAILOR PROGRAMS: By highlighting areas of strength and weakness, test results allow the physician to tailor a program to the individual.

MONITOR PROGRESS: Repeating the tests at intervals documents changes achieved.

MOTIVATE PARTICIPANTS: The goal of improving from one test to the next serves as a strong motivator to stay with a program that offers this prospect.

The preparation for the 2,462 person study linked near the end of the scientific details section led to the development of the H-SCAN Functional Age test which measured the 12 candidate biomarkers for the study. The H-SCAN test pioneered the measurement of functional age in Age Management Medicine practices, and worldwide it is the most widely used system for that purpose. The H-SCAN based article in the Journal of Gerontology is the only study for selection of a panel of functional biomarkers of aging cited by the 2004 biomarkers article from the Journal of Gerontology, also linked in the scientific details section. The biomarkers are:

   Auditory reaction time
2.   Highest audible pitch
3.   Vibrotactile sensitivity
4.   Visual reaction time
5.   Muscle movement speed
6.   Lung: forced vital capacity
7.   Lung: forced expiratory volume, 1 sec
8.   Decision reaction time
9.   Decision movement speed
10. Short Term Memory
11. Alternate button tapping
12. Visual accommodation

In a clinical setting, instruments can provide a measurement of these functions and can combine the scores into an estimate of functional age that the doctor can use to tailor a program for the patient. In the H-SCAN, a console connects to a PC computer or laptop. The remaining instruments connect to the console. These include buttons for tapping and reaction, a viewer with computer controlled lenses, high-fidelity headphones, a vibrometer to measure sense of touch and flow sensors that connect to the spirometer built into the console. The results are displayed in printable charts.

Automatic test administration

H-SCAN tests are designed to be self-administering – meaning that no staff is needed to do anything but bring the participant to the instrument and enter a few items of information. Besides saving staff costs, the object has been to achieve greater reproducibility of data through uniformity of procedures and instructions. Differences in the quality of instructions provided by different technicians are eliminated.

H-SCAN hardware is connected to a computer. Easy-to-follow instructions for doing the tests are presented by an on-screen instructor in movie format (participants need no familiarity with computers). Error-checking features incorporated in the program monitor every move and provide further instructions as needed to assure that each procedure is correctly performed.

Movie-clip instructions

In 50 short movie-clips, the software-resident instructor verbally explains each of the 12 tests and, with the help of an on-screen assistant, demonstrates exactly how to perform each test. Testing time averages about 45 minutes for the 12 tests.

There are extensive and interesting details on how specific functions decline with age. These can be seen in the second half of the 2462 person study by clicking on the link to the study at the end of the Scientific Details section of this article.

There is more information on the H-SCAN at this link: Anti-Aging Medicine and the H-SCAN.

Scientific Details

The investigation of methods for the measurement of functional, physical or biological age began at least 25 years ago. Possibly the most inclusive recent effort to understand biomarkers of aging and biomarker measurement technologies was the workshop that generated the article, “Biomarkers of aging: from primitive organisms to humans. Journals of Gerontology. Series A,. Biological Sciences and Medical Sciences 2004 Jun;59(6):B560-7.” The article states: “This is at least the third workshop on Biomarkers of Aging. In 1981, the National Institute on Aging (NIA) organized its first conference on "Nonlethal Biological Markers of Physiological Aging." A second workshop, also sponsored by the NIA, was held in 1986 in Chicago, Illinois.” A 10 year initiative followed from 1988 to 1998 and resulted in many publications. The article states: “...but it appears that a definitive panel of biomarkers for assessing physiological age of individuals within a population was not achieved.”

The article was based on an interdisciplinary workshop cosponsored by the International Longevity Center-USA, The Ellison Medical Foundation, Kronos Longevity Research Institute, the Institute for the Study of Aging, and Canyon Ranch Health Resort. The meeting was organized by Robert Butler and Richard Sprott, and the participants included several individuals involved in the 1988–1998 Biomarkers Initiative (Richie Feuers, Michael Forster, William Sonntag, and Norman Wolf), several gerontologists not involved in the 1988–1998 Biomarkers Initiative (Jeffrey Bland, Michael Hewitt, Gerald McClearn, Richard Miller, James Nelson, Arlan Richardson, and Richard Weindruch), and several clinicians (Howard Fillit, Mitchell Harman, Mark Hyman, Kathleen Johnson, and Evan Kligman).

Among the methods discussed to measure biomarkers were blood samples, anthropometric measurements, imaging techniques, and biopsies skin, muscle and fat. Nuclear MagneticResonance (NMR) can study the changes in anatomy and metabolic activity in the brain and other tissues. Positron Emission Tomography (PET) can study the neurochemical changes that occur in the brain during aging, including changes in neurotransmitter receptors and neurotransmitter synthesis, noninvasive imaging of reporter gene expression in living animals. Using PET reporter genes and PET reporter probes, investigators can examine the transcriptional activity and activation of promoters incorporated in transgenes or in viral vectors. There is the potential development of imaging technologies to non-invasively measure levels of reactive oxygen species (ROS) in tissues and groups of cells in real time.

After the discussion of the various potential biochemical biomarkers of aging, the article states the practical necessity for functional biomarkers of aging:

“In the absence of a more complete understanding of the mechanism of aging, clinicians would like to have age-related biomarkers that have adequate predictive value to provide qualified information to their patients to help improve organ-specific function throughout the life cycle and reduce unnecessary morbidity and premature mortality. These biomarkers might be more than disease risk factors and represent individual indicators of functional status. Clinicians might prefer a panel of functional biomarkers of aging that relate to health span.

“Such a set of putative functional biomarkers of aging could be measured in a large group of aging adults at an age where functional loss is known to occur most rapidly, such as in the 60 to 70 age group, but it would also be useful to have data on younger adults. ... The optimal goal would be to obtain a panel of functional biomarkers of aging usable for developing personalized medicine or other interventions that effectively reduce morbidity and improve organ-specific function, thereby delaying the necessity for costly hospitalization or social support of the aging population. At least one such attempt to do this has already been reported (55 [Hochschild R. Can an index of aging be constructed for evaluating treatments to retard aging rates? A 2,462 person study. J Gerontol Biol Sci. 1990;45:B187-B214.])”

In the cited study, Richard Hochschild, a physiologist educated at Johns Hopkins University and the University of California at Berkeley (MA) suggested 12 candidate functional biomarkers of aging. As stated earlier, unlike blood and some of the other tests, whose relevance is often based on theory, it is more evident that changes in memory and other cognitive functions, lung function, reaction time, hearing, touch, vision, muscle movement speed, etc. are part of the aging process. What is universally recognized as aging, apart from appearance, is the loss of ability to function.

Below is the abstract:

Journal of Gerontology: BIOLOGICAL SCIENCES, 1990,Vol. 45, No. 6, B187-21
Copyright 1990 by The Gerontological Society of America

Can an Index of Aging Be Constructed for Evaluating Treatments To Retard Aging Rates? A 2,462 Person Study
Richard Hochschild

Biomarkers of aging are needed to evaluate proposed treatments to retard aging rates. At present, the only validated biomarker of aging is maximum life span, which remains impractical for human use. Identification of other biomarkers awaits development of a method of biomarker validation. This paper outlines an approach for this purpose intended for selecting biomarkers usuable in humans. Prospective biomarkers are validated and weighted according to their correlation with interventions that, in healthy individuals, influence life span, namely mortality risk factors. A general mathematical method is presented for combining biomarker scores into an index of aging rate. This method addresses problems encountered with the traditional (multiple regression) method of calculating biological age and develops an index termed standardized biological age, SBA. In applying the method to 2,462 office workers, SBA, based on 12 physiological tests under investigation as biomarkers of aging, was found to depend on most of 17 surveyed dietary, exercise, life style, and geographical risk factors for mortality or health, suggesting that many risk factors predict rates of common functional declines with age. The 12 candidate biomarkers of aging in this study differed widely in validity according to the criterion employed. The approach holds promise for assembling an experimentally useful battery of biomarkers of aging.

The following is among the conclusions at the end of the study:

"It is reasonable to argue that the aging process is too complex and too limitless in its diversity of expression to be defined by a battery of biomarker tests, whatever its size. Ludwig (1989) responds to this argument with the suggestion that 'in science, not only pure reason governs, but also common sense (Max Planck), and common sense tells us that if the rate of progress of a variety of unrelated markers that correlate with chronological age is demonstrably decelerated by a given experimental variable (e.g., caloric restriction), the role of aging of the entire organism ... has been modified too.' Ludwig suggests that a relatively small number of biomarkers can be representative of many and that it is unnecessary to look at the full spectrum of age changes to know what is going on. The results of this study support that view."

In another forum, Mr. Hochschild has also stated:

"In clinical evaluations of individuals, sources of data variability must be taken into account, and longitudinal measurements, comparing the individual to him/herself over time, are generally more appropriate than comparisons to norms. Like most other physiological tests, the H-SCAN tests are subject to sources of unwanted variance, both between individuals and in the same individual over time. Depending on the test, these arise from differences in alertness, fatigue, some disease conditions, and from other sources. Inborn differences are a notable source of inter-individual variance. Individuals are born with different functional potentials. At an age of peak function such as 25 or 30, people differ dramatically in cognitive functions and virtually every other measure we can devise, and these inborn differences may or may not have anything to do with aging rate.

"Do individuals whose composite biomarker score is below normal necessarily age more rapidly than individuals whose score is above normal? Not necessarily. In individuals, it is the rate of functional changes over time that is the appropriate determinant of functional aging. In scientific studies, variance usually is controllable and most sources of variance average out between groups."

Elliott C. Small, A.B., Biochemical Sciences, Harvard College, is the founder of Centers for Age Control, which provides products and services to Preventive Health and Age Management Practices and large employers including health risk assessment programs, workplace medical claims reduction programs based on establishment of workplace wellness programs utilizing personal wellness profile software and the H-SCAN.
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