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I.R.F. / Aging news / General / 06081901

Aging: a Scientific Release of the Problem
Posted on: August 19, 2006

A scientific release of aging problem is reviewed. What is aging after all? How to reduce the aging and reach the longevity? What is the goal of anti-aging medicine? How and why do we age prematurely? Can gene therapy and stem cell therapy be used as anti-aging treatment? The understanding of history of aging problem, theories of aging, pathophysiology and pathology of aging, as well as possible treatment programs could answer all these questions.

Long before the fountain of youth, mankind has had an interest in staying young. As we move into the 21st century, that interest has not only continued, but it has become an obsession. While no one can really prevent normal, chronological aging, there are things we can do to slow down "pathological aging." After all, aging is about accelerated inflammation, depletion, and wear and tear. With the marked increase in life expectancy and life span, clinicians need to be aware of the effects of aging on the provision of treatment modalities. Appropriate interventions individualized to the patient can help to "compress morbidity" by shortening the period of functional decline common in old age. Therefore, the "health span" will come closer to matching the life span.

Disease and disuse are far more likely explanations for functional decline and the onset of common chronic conditions in older persons than is "true" natural or normal aging. Regardless of your genetic inheritance, you can accelerate or reduce aging by lifestyle choices and environmental conditions to which you expose your genes. There are even ways to reverse the problems associated with aging. Getting older does not have to mean growing older. Welcome to the world of preventative gerontology, better known as anti-aging medicine!

Until quite recently, the notion of reversing human aging was mere fantasy, absent of any scientific support. Throughout history, going as far back as the Epic of Gilgamesh 4700 years ago, we have dreamed of being able to cure aging and the diseases that accompany it; but every claim of a "fountain of youth" has proved to rely on nothing more than false hopes and – more often than not – an urge to profit at the expense of the gullible. The fact that we never really understood aging made it extremely unlikely that we could learn to slow, prevent, or reverse the process.

History and Aging

Today, we stand at a unique point in history, much like where we were in 1870 with regard to infectious disease. At that time, few had heard of Pasteur or Koch, and well-known scientists ridiculed the idea of microbes being dangerous or causing disease. Time passed, however, and, once ridiculed or not, we now take the concept of infectious disease for granted. In fact, much of what is good about modern medical care – sterile technique, antibiotics, immunizations, for example – derives from this single, powerful conceptual revolution that began 135 years ago.

Before we came to grips with the fact that microscopic creatures could harm and even kill us, effective intervention in most common diseases was also fantasy. In those days, treatment for tetanus infection – "lockjaw" – was a matter of early cauterization to remove "devitalized tissue" (using a red-hot iron rod or boiling oil), amputation (without anaesthesia) if things got worse, followed finally by hope and prayer, though nothing really improved the deadly outcome. We think of malaria, cellulitis, tetanus, pneumonia, and yellow fever as a short list of infectious diseases; to the physicians of those times, each of these diseases was independent and unique, without shared mechanism and without hope of effective treatment. Today, we have much the same conception (and misconceptions) of aging and age-related diseases. We think of cancer, atherosclerosis, osteoporosis, osteoarthritis, skin aging, and immune senescence as all unrelated, except chronologically. You get these diseases as you get older, not because they have anything in common, but "just because you get older." Even pathologists rarely consider common mechanisms, cellular events that link each of these diseases at the genetic level. After all, what could osteoarthritis and atherosclerosis, aging skin and Alzheimer’s possibly have to do with one another except that they happen to old people? Yet, not only do they have a great deal in common, but also it is precisely this common thread that will allow effective intervention both in age-related diseases and in aging itself.

Theories of Aging

Many theories of aging have been proposed, yet science has not produced a universal theory of aging. Why do we age? Current theories of aging at the cellular and molecular level generally revolve around two themes: aging is programmed, and aging is accidental.

To better understand the process of aging we need to focus on the differences between "normal" aging and "pathological" aging. Pathological aging is the aging process that is brought on by the presence of disease, such as adult-onset diabetes or arthritis, and that may later bring on cardiovascular disease or osteoporosis. This is not considered normal aging. These conditions are due to heredity or lifestyle. However, developing cataracts is considered normal aging, because if you live long enough, you will develop them. Every time the earth circles the sun, we are one year older chronologically, yet we know that the rate at which people age biologically varies widely. The loss of muscle tone, circulation, immune capacity, skin elasticity and joint flexibility, for example, occurs much more quickly in some people than in others. This is due to gene expression. Genes do not change, but their expression does:

[genotype] + [(diet, lifestyle and environment)] = [phenotype]

Therefore, we are not prisoners of our genetic destiny. There is a level of plasticity in gene expression. There is a large paradigm shift that needs to occur in our thinking: aging is a disease that can be prevented or reversed. Changing variables that affect genes such as diet, lifestyle, and stress can have an impact on genetic expression. We age because our hormones decline; our hormones do not decline because we age. Here we need to remember that hormones are required to trigger genes in cells to manufacture the necessary proteins, peptides, and other hormones. Lower volumes will yield lower manufacture.

The goal of anti-aging medicine is to increase the health span, not just the life span. After all, who would want to live longer with chronic debility or cognitive impairment? Anti-aging medicine consists of modalities and therapies involving diet, nutrition, exercise, destress, functional balance, system reserves, and a balance in anabolic to catabolic metabolism. Some of the familiar modalities of biochemistry and pathology associated with anti-aging medicine include glycation, inflammation, oxidation, methylation, endocrine deficiencies and imbalances, and decline of immunity. Aging is fundamentally a metabolic process. While clinicians deal constantly with the myriad symptoms of aging, the best results are not obtained until the underlying decrease in anabolic metabolism has been corrected.

Pathophysiology

As humans age, all functions and characteristics are modified. However, there is no clear consensus about what aging actually is – what "naturally" occurs with the passage of time – versus the effects of disuse and disease. Optimal health management requires an understanding of aging processes that are assumed to be natural and inevitable, and knowledge of the most accepted theories of how and why we age prematurely, usually due to many reversible risk factors.

Although at present there is a significant emphasis on development of new technologies, especially in the area of human genomics and stem cell research, to provide greater clarity on genetic and cellular aging mechanisms, adaptation of traditional, allopathic, complementary, and alternative integrative modalities to reflect current understanding of the effects of aging and of how to postpone or prevent premature aging is now possible.

Earlier studies attempted to identify the effects of natural or normal aging free of disease as distinct from the development of age-related diseases such as cancer, cardiovascular disease, diabetes, osteoporosis, and neurodegenerative diseases such as dementia and Alzheimer’s disease. Results from such studies suggest that the effects of aging are extremely "plastic" and variable from person to person. McEwen’s concept of the "allostatic load" suggests that each person’s signature of aging is a result of interactions among genetic makeup, lifestyle, diet, and environmental challenges. Thus, a combination of holistic parameters can be used to assess cumulative physiologic and psychological challenges over the life span and to predict how today’s health care practitioners will respond not only to new challenges such as management of age-related conditions and application of treatment modalities in old age, but also to longevity itself. Accordingly, a broader pattern of aging processes or biomarkers should be considered in determining how "well" a particular person is aging and how to customize interventions to reduce the effect of a chronic condition, thereby preventing certain processes from leading to the development of one or more ailments that are more likely to appear in old age. The list below shows various physiologic biomarkers found more often with suboptimal aging:

  • loss of strength;
  • reduced flexibility;
  • decreased cardiovascular endurance;
  • increased body fat (and resultant loss of lean muscle mass, or sarcopenia);
  • reduced resting energy expenditure;
  • lower kidney clearance;
  • reduced cell-mediated immunity;
  • increased hearing threshold;
  • reduced vibratory sensation;
  • compromised near vision and dark accomodation;
  • reduced taste and smell acuity;
  • increased autoantibodies;
  • altered hormone levels.

Another finding, from longitudinal studies, is that normal aging appears to be a phenomenon of gradual rather than precipitous change. Rapid decline is more likely to occur with the onset of a specific age-related pathologic process.

Treatment Programs

With the onset of the 21st century, it is apparent that we stand on the horizon of a revolution in anti-aging therapies and technologies. One of the most promising techniques that within the next 5–10 years will allow us to markedly expand the quality of health and human longevity is the concept of stem cell treatments. Recent advances by major corporations, both private and public, have documented that we are already capable of taking what are termed stem cells from an individual and selectively copying these cells along with their DNA components to restore the rejuvenative properties that our bodies lose as we age. This revolutionary technology of therapeutically cloning our own cells and giving them back to our cells will allow us to selectively focus on the components that deteriorate with the aging process, uniquely for each individual. We all inherited certain genetic weaknesses – some a poor immune system, some a poor nervous system, some a poor cardiovascular system. With these new technologies we will be able to selectively restore these faulty genetic mechanisms.

Source: B. Anton, L. Vitetta, F. Cortizo, and A. Sali; Can We Delay Aging? The Biology and Science of Aging; Ann. N.Y. Acad. Sci. 1057: 525–535
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