Читать книгу The Principles and Practice of Antiaging Medicine for the Clinical Physician - Dr. Vincent C. Giampapa - Страница 23

Biomarkers can be organized into a number of different categories^3–8 (Diagram III-5). For the purposes of this book, they are viewed with relevance to the aging equation.

Objective biomarkers are biomarkers that are measurable by laboratory methods and standardized testing protocol. These include the following:

1. Hormonal panel.

2. Glycation, inflammation, oxidation and methylation panel.

3. Cardiovascular laboratory panel.

4. Immune panel.

5. Bone metabolism panel.

6. Brain metabolism panel.

7. Ultra Fast CT Heart.

8. Body Mass Index and pH level.

9. Body Composition Data.

10. Computerized H-Scan Screening Marker^* (Diagram III-6).

11. Aerobic capacity and flexibility.

12. Vital signs.

13. Gene banking markers.

14. Bone density scans.

Objective biomarkers are hard data, which are measured and documented with standardized and accepted laboratory parameters and technology. Objective data and biomarkers can be viewed as direct measurements of altered gene expression; that is, changes in the functions of genes and their subsequent protein production are responsible for creating the molecular changes that we see within our objective data measurements.

Subjective biomarkers are revealed by specific questionnaires describing age-related symptoms and body changes. They are indirect measurements of gene expression. The questionnaires include the following:

1. A general subjective questionnaire, which reveals key symptoms of age-related diseases.

2. A family health questionnaire, which is used to screen for genetic tendencies most likely to be inherited by a patient and most likely to manifest themselves in a given environment within a given lifestyle.

3. A personal health assessment risk questionnaire, which is used to evaluate the patient’s lifestyle, behavioral tendencies and “personal environment” within which his or her genetic potential is expressed.

Subjective biomarkers, in general, are a reflection of indirect secondary gene expression changes; that is, they are measures of the symptoms and effects a patient may sense or feel, which are related indirectly to the molecular and genetic changes that are the origin of these findings.

Photographic documentation is an extremely important tool in a comprehensive age-management evaluation. It is the final physical representation, which can be seen as the combined effect of the underlying secondary and primary genetic expression changes that have occurred during a patient’s lifetime.

Another and more convenient way of looking at biomarkers of aging is in determining which are modifiable and which are nonmodifiable. Nonmodifiable biomarkers are genetic characteristics that cannot be modified by diet, pharmaceuticals, nutraceuticals or lifestyle at present. This includes body height, bone length, etc. Modifiable biomarkers are biomarkers that respond relatively quickly to changes in lifestyle and diet and to environmental changes. For instance, decreased muscle mass and aerobic capacity are strongly correlated with lower biological functional age. But they are also some of the key biomarkers that can be improved quickly with changes in exercise and with diet and nutrition programs.

Dr. Ward Dean described other biomarkers in his book The Biological Aging Measurement—Clinical Applications.⁹ For instance, muscle strength, basal metabolic rate, body/fat ratio, glucose tolerance, cholesterol, high-density lipoprotein (HDL) levels, blood pressure and bone density are also modifiable biomarkers that respond well to changes in lifestyle interventions, including changes in diet, nutrient supplements and prescription medications.

In the future, many more modifiable biomarkers are sure to be identified; they include gene banking (Diagram III-7). This topic is discussed in the final chapter of this book, “Anti-Aging Technologies: Present and Future Trends.”

For the cosmetic surgeon interested in presenting to a patient a simple but effective anti-aging program, or age-management system, it is important to choose the biomarkers that are most easily measurable and yet most informative.

In accordance with anti-aging clinical goals—that is, emphasizing maintenance of optimal DNA function by decreasing DNA damage, increasing DNA repair, augmenting the immune function, and optimizing gene expression—a core or basic anti-aging program can easily be established.

First, however, why are these clinical goals important? Maintaining optimal DNA function as a primary goal for an age-management program is the essential concept in any anti-aging program.

It must be remembered that the reason why people do not reach their full health and longevity potential is not because their DNA is faulty but because their DNA repair processes are. This results in poor genetic copies within each generation of cell populations, causing mutations in proteins and errors in enzyme production. These processes induce apoptotic pathways to cell programs to kill abnormal cells and also interfere with stem cell pool reserves. They continue until selected organ systems fail and people lose functional organ reserve (Diagram III-8) and, eventually, die.

It is also essential to keep in mind the effects of today’s progressively hostile environment, which also causes more oxidative stress (more free radicals), as well as damage to both nuclear and mitochondrial DNA banks. This contributes to loss of both health and longevity, as well as the physical changes¹⁰ that cosmetic surgeons have been trained to observe and operate on with cosmetic procedures (Diagram III-9).

The consequences of poor DNA repair become quite obvious in view of the sequence of events with both adequate and inadequate DNA repair mechanisms (Diagrams III-10 and III-11). If the repair of DNA damage is complete, a person basically maintains the optimal use of his or her inherited genetics, and little or no disease manifests itself for a relatively long period of time. If this repair process is incomplete, then genetic deficiency, or poor gene expression, is present, along with biochemical inhibition, and this results in mutagenic and toxic disease processes (Diagram III-12).

The effects of a toxic environment can also be seen. It is, again, vitally important to keep in mind that the main goal is to improve modifiable biomarkers of aging and to be able to document these changes with appropriate laboratory and subjective data. Not all genetic potential is easily modifiable; therefore, not all biomarkers can be improved, at least at this time.

For the cosmetic surgeon, the easiest way to monitor modifiable biomarkers of aging is to use an office-based biomarker test kit which measures DNA damage rates. These rates are obtained by measuring changes in 8-hydroxy-2’-deoxyguanosine levels, which is the standard test for measuring DNA damage inside the cell nucleus. The second most effective and targeted biomarker, also available in the office test kit format, is the measurement of lipid peroxidation, which is a direct reflection of free radical oxidation, or damage to the lipid cell membrane. This test involves measuring 8-epi prostaglandin F_2α levels from the urine or blood. This, in essence, gives an idea of the general level of free radical damage present and active.

The ability to document marked drops in both DNA damage and free radical levels with these two tests forms the hallmark of a core anti-aging program for the cosmetic surgeon. The significance of these two biomarkers has been discussed in Chapter II on theories of aging. The ease of sampling through blood or urine tests, as well as the ease of monitoring the resulting two values, has been positively correlated with marked improvements in quality of health and sense of well-being.¹¹

Other key modifiable biomarkers that can be measured are changes in degrees of the four key concepts mentioned previously in the aging equation: rates of glycation, methylation, oxidative stress and inflammation. Improvements in these laboratory data are also directly related to overall improvements in gene expression occurring at the cellular level and directly affect cell signaling.

In summary, for the cosmetic surgeon, an introductory anti-aging program, or age-management evaluation, needs to consist of nothing more than measurement of and a therapeutic improvement in the following biomarkers:

1. DNA damage.

2. Free radical levels.

3. Physiological changes, as documented by a symptom-related questionnaire (see Resource section).

This simple approach can have a tremendous impact on aging efficiency (Diagram III-13). With specialized physicians actively involved in a more comprehensive anti-aging program and evaluation, a much more comprehensive and exhaustive list of subjective, objective and modifiable biomarkers should be compiled in an overall evaluation. This book does not present details of a comprehensive evaluation, because that requires a degree of knowledge and time commitment that most busy cosmetic surgeons and physicians do not have. Instead, this book presents the format for an essential core biomarker evaluation that can be used in a cost-efficient manner and can give an age-management program as much credibility and effective impact as possible for the busy cosmetic practice.

Along with the use of these key biomarkers, an overall age-management program should include essential key anti-aging supplements^12–30 to accomplish the key goals previously discussed. With the right balance of nutraceuticals, it is possible to markedly improve key modifiable biomarkers, as follows:

1. Decreasing DNA damage rates.

2. Increasing DNA repair rates.

3. Improving immune function.

4. Regulating the key concepts of the aging equation: the processes of glycation, methylation, oxidation and inflammation.

This approach also helps balance the biorhythmic cycle and pattern of the autonomic nervous system and aids in regulating hormonal release patterns.

Further improvement in the assimilation and use of basic food nutrients ingested with each meal can be accomplished as well by aiding the digestion with the right digestive enzymes and supplemental intestinal flora support.

Improvement in the pH levels of both the extracellular matrices (“cellular soup”—that is, the fluid around the cells) and the intracellular matrix (the fluid within the cells) markedly enhances the biochemical efficiency of the cell machinery and improves the aging process at this microscopic level.

Another main concept to keep in mind is the delivery of these supplements throughout the day: that is, a phased delivery system. The use of as many naturally occurring plant and enzymatic complexes as possible, rather than synthetic supplements, is also important. It will be made clearer later that the natural components in products are much more effective than synthetically manufactured or designed supplements.

In summary, the overall effects of this nutraceutical approach are as follows:

1. Improved gene expression³¹ (Diagrams III-14 and III-15).

2. Improved quality of life.

3. Improved modifiable biomarkers of aging.

4. A noticeable effect and improvement in the overall physical signs of aging that plastic surgeons recognize.

Since the early 1990s, this strategy has been shown to be very successful in all patients who have been treated with this approach.

It is, without question, time to realize that this information and these simple laboratory tests are at physicians’ disposal to improve the well-being of patients’ quality of life, as well as their overall physical appearances.