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THE OXIDATIVE-DYSOXYGENATIVE MODEL OF AGING
Majid Ali, M.D.

OUTLINE
I. Introduction
II. Spontaneity of Oxidation and Aging
III. The Cross-Linkage Theory of Aging
IV. The Free Radical Theory of Aging
V. The Immune Theory of Aging
VI. Rates of Oxidation and the Length of Life Span
VII. DNA Repair as a Function of Life Span
VIII. Life Extension by Caloric Restriction
IX. Life Extension by Genetic Modulation
X. The Oxidative-Dysoxygenative Model of Aging
XI. Implications of the Oxidative-Dysoxygenative Model
XII. Closing Comments

I. INTRODUCTION

The human frame ages when its body organs age. The organs age when their tissues age. The tissues age when their cells age. The cells age when their molecules age. Molecules age when they lose their plasticity. How do molecules lose their plasticity? By oxidative injury. What provides the primal oxidative drive? Primarily oxygen in human biology. At that level, oxidative molecular damage driven by oxygen—and perpetuated and amplified by spontaneity of oxidation in nature—may be seen as the basic mechanism of ongoing molecular aging.1 However, Nature has been preoccupied with energetic and molecular complementarity and contrariety for a long time. One could hardly expect that simplicity to remain unchallenged for too long.

Oxidation is nature's grand design for assuring that no life form lives forever.1-4 O xidation in nature is a spontaneous process. It needs no external cues or outside programming. It requires no expenditure of energy. This essentially is the Second Law of Thermodynamics applied to the subject of the fundamental injury-healing-injury cycle of life. In the chapter on dysoxygenosis in this volume, I furnished the simple analogy of a boy playing with a ball attached to a string. The boy twirls the string overhead to move the ball in an orbit defined by the length of his arm and the string. The string keeps the ball from flying away until it breaks. In an analogous way, electrons spin around the nucleus of an atom, held in their orbits by the nuclear pull. The electrons 'fly away' when the nuclear force is not strong enough to hold on to them, or electrons are pulled away by a force stronger than the one that keeps them tethered to the nucleus. A clear understanding of those elementary electron dynamics must form the foundation for all concepts of aging.

In this chapter, I present a brief survey of various existing theories of aging and outline some extraordinary insights into the aging process provided by recent and elegant experimental work. The results of studies of changes in the life span of Saccharomyces cerevisiae induced by varying growth conditions, gene deletions, and altered dynamics of transcription factors are challenging some long-standin

g assumptions concerning the role of free radicals in aging. Those findings also provide direct and strong evidence for the oxidative-dysoxygenative model of aging presented previously in Oxygen and Aging.5

II. SPONTANEITY OF OXIDATION AND AGING

In 1983, I put forth my spontaneity of oxidation (SO) model of aging.1 Succinctly stated, the theory holds that aging involves loss of energy triggered, perpetuated, and completed by the ongoing and spontaneous loss of electrons in all human cells and body. In 2000, I presented my oxidative-dysoxygenative model of aging in Oxygen and Aging as an extension of the earlier SO model. Simply stated, that theory holds that the primary aging process involves dysoxygenosis, so that cells, tissues, and body organs age because they cannot maintain oxygen homeostasis. For the general readership, I introduced the term dysfunctional oxygen metabolism for dysoxygenosis.6,7 The essencial difference between the 1983 and 2000 models is this: In the former, the focus was essentially on the primal oxidative drive provided by spontaneity of oxidation in nature—and the degradative consequences of free radical generation triggered, amplified, and perpetuated by the phenomenon. By contrast, the emphasis in the oxidative-dysoxygenative model is on both the regenerative and degradative characteristics of oxygen and oxygen-related factors.

In 1983, at the time of proposing the SO model of aging, there were three major and some other lesser- known theories of aging. The major theories included: (1) Johan Bjorksten's protein cross-linkage theory of aging8; (2) Denham Harmon's free radical theory of aging9; (3) and Roy Walford's immune theory of aging.10 It seemed necessary to consider how well the proposed SO model of spontaneity of oxidation—providing the primal metabolic drive for the aging process—might stack up against the three existing major aging theories proposed earlier. Even a cursory look at the cross-linkage, free radical, and immune theories made it clear that what I was proposing was fully consistent with all three. Indeed, my model represented an extension of those theories in the sense that it provides a clear underlying mechanism for all three. Below, I include some brief comments about each of those three theories.

III. THE CROSS-LINKAGE THEORY OF AGING

In 1955, Johan Bjorksten proposed his cross-linking theory of aging.8 According to this theory, the basic aging process involves accumulation of damaged and insoluble (cross-linked) proteins, DNA, fats, and other large-sized molecules, such as vitamin A. Such cross-linked molecules cause aging by impeding or blocking the actions of enzymes, vitamins, and other substances. The process of cross-linking may be illustrated as follows: The structure of many healthy proteins resembles long threads of different sizes. Under heat or chemical stresses, individual molecules are bent, turned and twisted into many different shapes. Such misshapen molecules quickly regain their original shapes when the stresses subside. The term cross-linking means that such turned and twisted molecules get permanently disfigured because of excessive stress. Thus, such molecules are torn apart and, when the ends unite, they get tangled with each other and form crooked protein molecules. Cross-linked molecules are two molecules wrapped around each other in such a way that neither can function normally. Since Bjorksten first proposed it, the cross-linking theory of aging has been fully validated.

In the context of the spontaneity of oxidation theory of aging, the crucial question concerning the cross-linking theory is this: What is the molecular basis of cross-linking? Extensive review of the literature over a period of two decadese—since putting forth the 1983 SO modele—has convinced me that all cross-linking that occurs during the aging process is oxidative in nature. I have not found any exceptions to that. And the primary drive for oxidation in human metabolism, as I indicate earlier, is spontaneity of oxidation in nature. Thus, the spontaneity of oxidation theory begins where the cross-linking theory leaves off.

IV. THE FREE RADICAL THEORY OF AGING

In 1956, Denham Harmon proposed his free radical theory of aging.9According to this theory, the aging process involves molecular and cellular injury caused by free radicals. Free radicals are highly unstable, extremely reactive atoms or molecules that form during normal metabolism, as well as during cellular injury caused by chemicals, microbes, radiation, and other types of injury. Since its introduction, the basic tenet of this theory was supported by an ever-growing body of data.11 Indeed, until recently, the case for this theory seemed iron-clad. In a later section of this chapter, I cite studies that have created a huge chink in its armor.

However, in the context of the spontaneity of oxidation theory of aging, the crucial question concerning the free radical theory of aging is this: Where do free radicals come from? How do such radicals cause molecular and cellular aging? And again, a broad survey of the literature over a period of two decades has convinced me that all free radical generation is fueled by oxidative triggers. Furthermore, all molecular and cellular injury caused by free radicals is oxidative in nature. There are no studies to the contrary. And again, the primary drive for free radical production, as well as injury caused by such radicals, is spontaneity of oxidation in nature. Thus, the spontaneity of oxidation theory extends the free radical theory of aging.

V. THE IMMUNE THEORY OF AGING

In 1962, Roy Walford proposed his immune theory of aging.10,12 According to that theory, the aging process involves injury to the immune system of the body so that the injured system becomes confused and turns on the individual. Specifically, immune injury results in the production of abnormal antibodies that injure the body's own tissues rather than fighting microbes. Such antibodies are called autoantibodies. Like the cross-linking and free radical theories before it, the basic claim of this theory has also been validated. For example, increased production of autoantibodies directed against various body organs occurs with advancing age. Furthermore, there is much direct evidence for cellular injury (and aging) caused by such antibodies.

The core question concerning the immune theory of aging is the same as for the two preceding theories: What causes the immune injury? What is the molecular mechanism that triggers autoantibody production? Once again, the examination of the available clinical and experimental evidence leads us to the same conclusion: the immune injury is caused by oxidizing chemicals, microbes, and other agents. And once again, the primary drive for oxidative immune injury is spontaneity of oxidation in nature. Thus, the spontaneity of oxidation theory also extends the immune theory of aging.

There are some other less-known theories of aging, including the following: (1) wear-and-tear theory; (2) preprogrammed senescence theory (the 'Commitment Theory of Cellular Aging.'); (3) rate of metabolism theory; and (4) limited cell division theory.13 A close examination of each of those theories also shows that it is equally compatible with the SO model of aging. It is clear from the basic facts of oxygen and oxidation presented here that the primary aging mechanism in the wear-and-tear, preprogrammed senescence, and rate of metabolism theories is oxidative injury. As for the genetically determined limited cell division theory, growing evidence seems to indicate that genes require optimal oxygen metabolism for proper functioning (discussed further in the following chapter). It seems safe to predict that future research will provide additional and conclusive evidence for that view.

VI. RATES OF OXIDATION AND THE LENGTH OF LIFE SPAN

Frozen meat left on a kitchen table thaws within hours and then begins to decompose. Such decomposition is the result of spontaneous oxidation and is called auto-oxidation. The same process occurs when tissues of animals are removed and allowed to undergo spontaneous oxidation and decomposition. The rate at which such oxidation occurs is called the rate of auto-oxidation and is an indicator of the rate of metabolism of the animal species. In other words, those rates of oxidation represent the natural (innate) capacity of tissues for self-destruction. If the spontaneity of oxidation theory is valid, the rates of auto-oxidation of various animal species would be expected to correlate well with their life spans. That possibility has been researched and the rates of oxidation in tissues of various animal species have been correlated with their life span.

Table 1. Rates of Auto-Oxidation and Life Spans of Mammalian Species 14
Species	Oxidation Rate	Life Span (yrs)
Man	24	90
Orangutan	25	50
Baboon	35	37
Green monkey	41	34
Squirrel monkey	74	18
Rat	104	4
Mouse	182	3.5

Researchers at the National Institutes of Health measured the rates at which tissues undergo spontaneous oxidation in over 70 mammals.14 They observed that the animal species which showed the highest rates of auto-oxidation had the shortest life spans, and those with the lowest rates of auto-oxidation had the longest life spans. There was almost a perfect inverse correlation between the rates of oxidation and the species life spans. Selected data for rates of auto-oxidation in selected animal species and humans are shown in Table 1.

The data in Table 1 illustrate clearly the inverse relationship between life spans and auto-oxidative rates: Animal species that oxidize their tissues rapidly live the shortest life spans, while those that oxidize their tissues slowly live the longest life spans. Man—with the lowest rate of tissue breakdown—has the highest longevity, while the mouse (which has the highest oxidation rate among the species listed in the table) has the lowest longevity.

VII. DNA REPAIR AS A FUNCTION OF LIFE SPAN

Deoxyribonucleic acid in cells is under unrelenting assault from disruptive influences. Fidelity in its structure and during its duplication is evidently crucial to cellular structural and functional integrity. That is assured by a stunning array of cellular enzymes that detect and repair deletions, additions, and translocations in DNA threads. Such enzymes not only remove damaged segments, but also rapidly reconstitute the DNA threads in areas of gaps left by the damaging agents. One would expect that the efficiency of such enzymes would diminish with age. That, indeed, turns out to be the case. At a basic level, this expectation is borne out by the observed rising incidences of various cancers with increasing age. That is clearly a reflection of things going awry in DNA repair.

The efficiency of DNA repair enzymes can be assessed by measuring the rate of consumption of such enzymes added to DNA damaged under control conditions (in which nucleotide are exposed to various DNA-damaging agents). That was the approach taken by Hart and Setlow in the early 1970s.15 They measured rates of DNA repair in fibroblasts from a number of species and plotted it as a function of the maximum life span of the species. Table 2 shows data for humans, Indian elephant, cow, golden hamster, Norwegian rat, field mouse, and long-tailed shrew. The numbers have been rounded to simplify the presentation of data.

True to its complementarian and contrarian disposition, Nature has also built elaborate systems to repair the systems that restore injured DNA. This subject is discussed in Nature's Preoccupation with Complementarity and Contrariety, the first volume of this textbook. 

Table 2. DNA Repair as a Function of Life Span 15*
Species	DNA Repair (relative)	Life Span** (logarithm)
Man	5	2
Indian elephant	4.3	1.9
Cow	4	1.5
Golden hamster	2	0.6
Norwegian rat	1.8	0.5
Field mouse	0.8	0.38
Long-tailed shrew	0.5	0.2

* All values are included as close approximations for the sake of simplicity.

** Life span is given as logarithmic value of the maximum species life span.

VIII. LIFE EXTENSION BY CALORIC RESTRICTION

Caloric restriction extends life span in many species and is the only established way of increasing the lifespan of mammals. Since Clive McKay's early classical work on effects of undernutrition (not malnutrition) on aging at Cornell University,16 an enormous body of literature has accumulated validating the direct relationship between caloric restriction and longevity.17-23 This linkage has been documented in yeast, mosquitoes, flies, and rats. To cite a specific example, the life span of Saccharomyces cerevisiae increases by 25% when the glucose level in the culture is reduced from 2% to 0.5%.22 Similarly mosquitoes on caloric restrictions live longer than those with ad-lib (unrestricted) feeding.

In experimental conditions, life span can not only be extended by limiting glucose availability, it can also be prolonged by reducing the activity of the glucose-sensing cyclic-AMP-dependent kinase (PKA). Such lifespan extension in mutant yeast requires both Sir2—a regulatory protein with regulatory influences—and nicotinamide adenine dinucleotide (NAD).23 I return to this subject in the next section.

IX. LIFE EXTENSION BY GENETIC MODULATION

The list of genes involved in the aging process is getting longer literally by the month. Life extension by genetic modifications has been verified in a large number of reports.24-34 Longer lives of mutant yeast, worms, and fruit flies have been documented with a large numbers of studies. Not unexpectedly, such lengthening of life span is accompanied by many serious adverse biologic consequences of genetic tinkering. In every species investigated so far, developmental and growth derangements have been documented, including loss of fertility. In 1999, Italian investigators published a landmark study in which life extension in mammalian species was achieved by p66shc gene modification.35 In this report also, mice had reduced fertility and serious pulmonary malformations were documented among other adverse effects. For those and other reasons, I do not share the enthusiasm of geneticists who are pregnant with the hope of extending human life span by inserting or deleting individual genes.

X. THE OXIDATIVE-DYSOXYGENATIVE MODEL OF AGING

In the past, it was generally assumed that the mechanism by which caloric restriction lengthens life span is by reducing the rate of metabolism and consequent free radical activity. Indeed, this was considered the major laboratory evidence for the free radical theory of aging. That view has been challenged by recent dissections of the genetic and molecular pathways of aging and life extension. Indeed, the results of some studies of the life span of Saccharomyces cerevisiae are turning the old thinking on its head and are providing impressive evidence for the oxidative-dysoxygenative model of aging. Specifically, it is now known that caloric restriction extends life by both increasing resistance to reactive oxygen species (ROS) and by diminishing the production of ROS.11

Since I proposed my oxidative-dysoxygenative theory in Oxygen and Aging5 in 2000, a number of elegant experiments involving varying growth conditions, gene deletions, and transcription factors have been performed to explore the roles of oxygen homeostasis and free radical dynamics involved in the aging phenomena. The major genetic pathways involving hundreds of genes in this context include the Sir2 family, cytochrome c1, and the transcription factor HXK2. The results of those investigations provide direct and strong evidence to support the oxidative-dysoxygenative model of aging. Below, I briefly summarize the results of some of those studies.

Sir2 Family of Regulatory Proteins

Sir2 is a family of proteins with important regulatory roles in aging.24-31 Specifically, this family links chromatin silencing, metabolism, and aging.24 In yeast aging—and most likely in aging of many other species—the chromatin silencing functions are critical to life extension. Caloric extension increases the activity of Sir2.21 Some members of this family function as longevity proteins with transcriptional silencing ability.25 The silencing protein Sir2 and its homologs are NAD-dependent protein deacetylases.26 Sir2 protein and its homologs contain a phylogenetically conserved NAD+-dependent protein deacetylase activity .27 The Sir2/3/4 complex and Sir2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Sir2 proteins also has a well-delineated role in life extension by calorie restriction in Saccharomyces cerevisiae. The effect of caloric restriction in this context also requires a role of nicotinamide adenine dinucleotide (NAD).

The changes in metabolic behavior of Saccharomyces cerevisiae in response to availability of glucose have yielded crucial information concerning the mechanisms involved in life span extension with caloric restriction. Measurement of respiration in caloric restriction experiments performed with wild-type and Sir2-deleted yeast revealed the relationships between caloric intake, Sir2 protein, fermentative-to-respitaory shift, and life extension.30 Glucose is metabolized to pyruvate, which serves as the bifurcative molecule for the respiratory and fermentative pathways. Respiratory breakdown of glucose to CO2 generates 28 ATP molecules per molecule of glucose, whereas fermentation of glucose to ethanol generates only two ATP molecules per molecule of glucose. This 14:1 energetic ratio is of great significance to the previously described state of oxidative regression to primordial cellular ecology.31 described in the preceding chapters. It turns out that S. cerevisiae actively adapts to the available glucose supply with major fermentative-to-respiratory shift. When glucose concentration is high, the yeast prefers fermentation. I furnished the analogy of spoiled teenagers at a family picnic table wasting food in an article on dysoxygenosis.38 By contrast, when glucose availability is low, the yeast shifts its metabolism to predominantly respiratory mode, extracting much larger amounts of energy from the scarce glucose resource.30 As indicated earlier, a 0.5% concentration of glucose produced a two-fold increase in respiration of the yeast compared to that of cells grown in 2% glucose concentration. That metabolic shift was accompanied by a 25% increase in life span. Experiments conducted with Sir2-deleted yeast showed absence of life extension under identical conditions of glucose availability, thus linking Sir2 to life extension obtained with caloric restriction.

HXK2

Additional support for the oxygen-related rather than free-radical-related mechanisms for life extension was drawn from the results of experiments with strains lacking HXK2—a gene that encodes one of the three hexokinases that introduce glucose into glycolysis.30 HXK2 deletion is known to extend life. Thus, it was expected to mimic the effects of growth in low-glucose medium, which it did. HXK2 deletion was found to also increase respiration. Transcriptional profiling of S. cerevisiae genome disclosed a highly significant overlap in the transcriptional changes induced by low glucose (0.5%) growth and that seen with HXK2 deletion.

Hap4 Transcription Factor

Another line of evidence for the central role of oxygen (the respiratory mode of ATP production by contrast to the fermentative pathway) in life extension is obtained from the results of experiments involving the transcription factor Hap4. This factor activates many genes involved with mitochondrial respiration.36,37 Transcriptional profiling reveals that many of those genes upregulated more than two-fold by Hap4 are involved in the metabolic switch from fermentation to respiration. In S. cerevisiae life extension studies, overexpression of Hap4 redirects the respiro-fermentative flux distribution, resulting in a switch of metabolism from fermentation toward respiration, and provides further direct evidence for the pivotal role of oxygen in aging.

Cytochrome C1

Further evidence for the role of oxygen in life extension was marshalled by experiments involving interruption of electron transport in S. cerevisiae, which was expected to abrogate life extension under the experimental conditions. That turned out to be the case as well. Yeast strains with deletion of the gene encoding cytochrome c1 (CYT1) failed to show life extension, indicating that metabolic shift to respiratory ATP production was a pre-requisite for life extension under the experimental conditions.

Finally, as indicated earlier, direct evidence against the free radical-induced aging process, at least in the context of aging of Saccharomyces cerevisiae, may be drawn from experiments showing that the lengthening of life span of the yeast with caloric restriction is associated with increased resistance to reactive oxygen species.24 This should not come as a surprise, since the free radical theory completely ignores the myriad roles of oxygen in redox regulation and oxygen homeostasis.

The above-cited recent studies of the fermentative-to-respiratory metabolic shift in yeast shed new light on the phenomenon of oxidative regression to primordial cellular ecology. When I initially described that phenomenon, I was preoccupied with the consequences of the respiratory-to-fermentative metabolic shift occurring in healthy human cells subjected to unrelenting oxidosis, acidosis, and dysoxygenosis.39 I had not fully appreciated that clinically significant metabolic shift in the opposite direction—fermo-respiratory shift—could also take place under certain conditions. The finding that Saccharomyces cerevisiae rapidly shifts to fermentative mode of ATP production in the presence of ample supplies of glucose is of considerable importance to clinicians like me. We have repeatedly observed how rapidly sugar or excess starches in the diet can trigger abdominal bloating, cognitive difficulties, and other symptom-complexes— symptomatology that may be readily explained on the basis of increased fermentation in the gut.

XI. IMPLICATIONS OF THE OXIDATIVE-DYSOXYGENATIVE MODEL OF AGING

It has been estimated that the 50 percent survival rate—the age reached by one-half of the population— increased from about 22 years in ancient Rome to about 40 years in the middle of the nineteenth century. In the United States, that number reached 49 in 1900. The 50 percent survival then showed rapid increases in this country, reaching 67 years in 1946, 72 years about fifteen years later, and leveled off at about 74 years in the 1980s.40 It seems safe to attribute such rapid rises in the 50 percent survival to improvements in agriculture, availability of food, vaccination, and public health measures. Clearly, the aforementioned theories of aging during those decades had been of theoretical interest only, since no concrete measures were taken to extend life span according to the dictates of any of those theories.

The imperatives of the oxidative-dysoxygenative model of aging, by contrast, are compelling. The incidence of oxidative-dysoxygenative energy disorders—fibromyalgia, chronic fatigue syndrome, environmental illness, Gulf War syndrome, the September Eleven-related illness, and others—is rising in nearly all countries with epidemic proportions. Recently, The Wall Street Journal estimated that fibromyalgia now afflicts over eight million Americans.40 Nearly one of every six women and men sent to the Gulf War in 1991 are now fully or partially disabled.42 The energetic-molecular basis of none of those maladies can be understood within the context of the prevailing disease classifications. Beyond that, the incidence of Alzheimer's disease in the older individuals and of cognitive difficulties in younger persons is rising at a frightening rates.

Below, I include some text from one of my articles published in The Journal of Integrative Medicine43 to show that we can learn much about dysfunctional oxygen metabolism from disappearing frogs, shrimp, oysters, and other living beings.

What do alpine meadows of Yosemite National Park, piney woods of South Carolina, and plains of Laramie, Wyoming, have in common? Answer: The warm summers there are unusually hushed. The reason for this is that the frog population in those areas—and many others in the world—has been decimated. By some estimates, up to a third of the nation's amphibians—frogs, toads, and salamanders —have disappeared. In 1988, in Costa Rica on a Monteverde ridge, half of the 40 amphibian species simply vanished. Some wags have speculated that those amphibians were stolen by aliens—a global whodunit!

In Chesapeake Bay, during some summers, nearly all Eastern oysters are parasitized by dermo. Up to one-half of the total population succumbs. Similarly, grass shrimp suffer from heavy parasitic infestation. In Alaska, ten years after one of the largest oil spills in history, the Valdez accident, species which have failed to recover include the common loon, cormorant, harbor seal, harlequin duck, and pigeon guillemot.

Marine biologists report "mass mortalities" among plants and aquatic life forms. Consider the following quote from a recent issue of Science44:

In the past few decades, there has been a worldwide increase in reports of diseases affecting marine organisms. In the Caribbean, mass mortalities among plants, invertebrates, and vertebrates have resulted in dramatic shifts in community structure. Recent outbreaks of coralline algae lethal orange disease have affected Indo-Pacific communities on unprecedented scale.

The oxidative-dysoxygenative model of aging is attractive for three reasons: (1) It has a strong explanatory power for a host of observed phenomena concerning the aging process as well as for several tenets of the competing models and theories; (2) It provides molecular underpinnings of newly emerging patterns of biologic derangements in wildlife; and (3) It calls for a sharp focus and vigorous efforts to undertake public health measures to preserve and/or restore redox and oxygen homeostasis to prevent disease and extend life span. The recently documented fermentative-to-respiratory metabolic shift in yeast calls for a careful assessment of our existing notions of man-microbe relationships, especially those observed in chronic oxidative-dysoxygenative energy disorders, such as fibromyalgia, chronic fatigue syndrome, environmental illness, Gulf War syndrome, the September Eleven-related illness, viral activation syndromes, chronic fatigue after chemotherapy for malignant tumors, and others.

References
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2. Ali M. The agony and death of a cell. In: Syllabus of the Instruction Course of the American Academy of Environmental Medicine. Denver, Colorado, 1985.
3. Ali M. Leaky Cell Membrane Disorder. Monograph. 1987. Teaneck, New Jersey.
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7. Ali M. September Eleven, 2005. New York, Aging Healthfully, 2002.
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26. Landry J. et al. The silencing protein SIR2 and its homologs are NAD-dependent protein deacetylases. Proc. Natl Acad. Sci. USA, 2000;97:5807-5811.
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41. Surgery on the skull for chronic fatigue? Doctors are trying it. The Wall Street Journal, November 11, 1999, pp, A1 and A8.
42. Navy News. September 13, 1995.
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Index of Article Authors
Majid Ali, MD
Omar Ali, MD
Mary Ann Carroll, RN
Alfred Fayemi, MD
C.Grieder-Brandenburger, RN
Judy Juco, MD
Tsuneo Kobayashi MD
Jean A. Monro, MB, BS
(This index is incomplete and will be completed shortly)

Past and
Current Editors
Omar Ali, M.D.
Robert Atkins, M.D.
Robert Bradford, D.Sc
Paul Cheney, M.D., Ph.D.
Steven Davies, M.D.
Alfred O. Fayemi, M.D.
Claus Hanke, M.D.
Doug Hutto, N.D.
Judy Juco, M.D.
Paris Kidd, Ph.D.
Oscar Kruesi, M.D.
Derrick Lonsdale, M.D.
D. Vijen Poleszynski, B.S.
Christine Radulescu, Ph.D.
Ray Russamono, M.D.
Susan Test, Ph.D.
Lowell Weiner, D.D.S.
John C. Williams, M.D.

The Journal of Integrative Medicine shall not be held responsible for statements of the contributing authors. The views and opinions expressed are those of the submitting authors and do not necessarily reflect those of The Journal of Integrative Medicine, The American Academy of Integrative Medicine,
The American Academy of Preventive Medicine, any advertisers or staff members of The Journal of Integrative Medicine
 

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The Journal of Integrative Medicine shall not be held responsible for statements of the contributing authors. The views and opinions expressed are those of the submitting authors and do not necessarily reflect those of The Journal of Integrative Medicine, The American Academy of Integrative Medicine, The American Academy of Preventive Medicine, any advertisers or staff members of The Journal of Integrative Medicine