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103. Glycoproteins and Aging

My recently published anti-aging book is available ftom the American Nutraceutical Association (205-980-5710).

Here are some excerpts:

1. The Biology of Aging: How we age

Introduction. As a new millenium dawns, we're closing in on our goal to end old age. Let’s face it! What we really want is to stay young forever, but even the most optimistic of us would agree - perhaps that’s an unrealistic hope. But there IS realistic hope for a long and healthy old age.

Anti-aging Research. So many discoveries about aging are popping up right now because there are currently thousands of scientists - geneticists, immunologists, gerontologists, molecular biologists, and others - who currently study how to increase longevity on dozens of fronts. Anti-aging medicine is a rapidly emerging clinical specialty. Biogerontology, the biology of aging, is a much-respected science today, and all of these researchers are making spectacular medical advances faster than at any other time in history. As a result, more people are living longer than ever before.

Middle Years. Much of the deterioration associated with "old age" can be slowed, stopped, and, in some cases, even reversed, with medical knowledge and technology that already exists today. In fact, the ranks of our centenarians - people more than one hundred years old - are already increasing, and are expected to double within the next five years. Life spans of more than 120 years are reasonably possible within the next 30 years. We’re well along in our quest to delay the onset of aging and give more of us more of those sweet middle years - from sixty to one-hundred-and-twenty!

Eye-of-Newt-Wing-of-Bat. It’s an exciting time, but it’s also a confusing time. There are hucksters hiding around every corner ready to peddle get-young-quick-eye-of-newt-wing-of-bat hoaxes to the lucrative senior market. I hope here to cut through this confusion and make clear the differences between phony claims and real scientific breakthroughs. As I’ve said, the reason I’m telling you all this is that I want you to know today how to live a long and healthy life for many more tomorrows.

Scientific Story. I want to tell you the story - a scientific story - of tested results and realistic promises that offer reasonable hope to anyone who’s getting older. Let’s begin with the basic biology of aging or, in other words, How do we age?

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Immortal Enzyme. In 1985, researchers began to drive the thin edge of the wedge under this intriguing question. They discovered an enzyme, now named telomerase, that can attach new telomeres to the ends of chromosomes each time a cell divides. In 1989, telomerase was found in an immortal line of human cancer cells. Since then, telomerase has been found in most immortal cancer cells but never in mortal cells. Telomerase doesn’t cause cancer. It merely allows cells to live forever. Well, what, do you suppose, are the implications of this?

Central Questions. This brief overview of the biology of aging leaves us with several questions regarding longevity, aging, and death.

  • Longevity. Why do we live no longer than we do?
  • Aging. Why do we grow old?
  • Death. Why must we die?

These are, in fact, the central questions. The first cuts at their answers were posed by some early, and provocative, views of aging - our next topic.

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2. Anti-Aging: Early Views

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Medicine is an Art. The practice of medicine is an art informed by science and bolstered by faith.

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Galen. Not inclined to modesty, the Greco-Roman physician Galen proclaimed himself to be the last word in medicine. And he was - for more than thirteen centuries.

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Cornaro. Then along came Luigi. Born around 1470, the Venetian nobleman Luigi Cornaro, ate, drank, and partied until about the age of forty and then, warned that he was about to drop dead if he didn’t change his habits, settled down to a simple life - eating lightly and exercising moderately. At age eighty-three he published one of history’s first how-to books, Discoursi della vita sobria, which translates as Discourse on the Sober Life.

Luigi’s Bestsellers. It immediately became a runaway bestseller. Encouraged, Luigi published a sequel to it at the age of eighty-six. And a third version at ninety-one. Luigi’s last book came out when he was ninety-five. And he lived for another several years.

Other Gifted Amateurs. Other gifted amateurs have contributed to our knowledge of the aging process. At about the time of Luigi Cornaro, as people began to ponder what caused aging to occur at all, an observant art student was dissecting cadavers to study their anatomy when he noticed that older veins are thicker. He guessed that this must increasingly restrict the flow of blood as a person aged, ultimately destroying life. The student was Leonardo da Vinci. His description closely matches the ailment we now recognize as atherosclerosis, or hardening of the arteries.

Paracelsus. Another notable of that era, Theophrastus Bombastus von Hohenheim, popularly known as the physician Paracelsus, was bringing the elixir-of-life branch of alchemy to the doorstep of science. Appointed professor of medicine at the University of Basel at the age of thirty-three, he proceeded to burn the works of Galen in public. Paracelsus pioneered the notion that diseases have chemical bases and so can be treated with chemicals (drugs). He also declared, however, that "all drugs are poisons," and that, "everything that man needs to maintain good health can be found in nature and it is up to science to find them."

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3. Anti-aging: Recent views

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Introduction. I’m going to tell you now about recent theories of how and why we age. So, let’s begin by reviewing our criteria for what makes a good theory. A good theory of aging must be able to explain four basic points. It must explain why the losses of healthy functions occur as we age; why they progress as we age; why they cannot be corrected; and, most importantly, why these losses are universal - that is, why the losses of healthy functions occur in all members of all species.

Wear and Tear. The old nineteenth century explanation for aging - the wear and tear that normal living inflicts on us - still sounds perfectly reasonable to many people even today. After all, isn’t that what happens to most of the familiar things that surround us, like washing machines and cars? It seems natural that our body's parts will deteriorate with use, begin to goof-up on the job, and eventually just fall apart. When enough parts have broken and can’t be repaired any more - no matter what medications, transplants, or other modern medical miracles are used - then the body, like any old washer or car, must be disposed of because, well, it dies.

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Flaws. The wear-and-tear theory of why we age, however, develops serious flaws once we start asking some tough questions about it. In this time of political correctness and rampant I-told-you-so behaviors, some people seem to take great joy when a famous Epicurean dies. See! See! That’s what he gets for sinful living - eating all that red meat, or smoking, or drinking, or sleeping around. These folks are missing the same obvious flaw in the wear and tear argument that the Puritans missed.

Sin. There’s a distressingly huge number of appallingly sinful people all around us living very long and healthy lives. And, sadly, many a pious, moderate soul has perished in the bloom of youth. The sinful-living theory simply doesn’t tally with what we all know. We all know, or know of, young people who live cautiously, eat careful organic diets, haunt health stores for the latest supplements, exercise, and maintain proper weight. Alas, we often find ourselves at their funerals when they fall prey to one of the so-called diseases of aging like cancer or heart disease.

Hardy Sinners. Then, perhaps, we meet the hardy ninety-year-old smoker, the attractive eighty-five year-old sun worshiper, and the ancient pastry chef, who’s excessively obese but obviously thriving. They all contradict the idea of the body as a machine. If the body could be destroyed by rough use, these people certainly gave it their best shot.

Descartes Notwithstanding *. Descartes* notwithstanding, our bodies are not machines in any ordinary sense. Machines don’t normally repair themselves or build new parts for themselves when old ones break. The machines we’re familiar with don’t constantly regulate their own internal balances. A machine can’t lower its energy needs when fuel is scarce and then, when it’s plentiful again, store it away for future needs. Most machines cannot do such amazing things, but (Hallelujah!) our bodies can.

Mates Making Others. Our bodies can also mate and make others - machines can’t! Our bodies can also make some of their parts get better with age, as when we exercise. What machine does that?

Fuel. So the wear-and-tear machine analogy simply doesn’t hold up very well under scrutiny. Your body is much more amazing than any machine, especially if you just help it along. But your body cannot perform these miracles without the stuff it needs.

Our Diets are Deficient. And here’s the rub. Our modern diets are deficient in six of the eight essential sugars (saccharides) that they need. These deficiencies cause our enzymes to function less efficiently than they should. Consequently, vital glycoproteins that we need are either built incorrectly or not built at all. The importance of glycoproteins in our diet cannot be overstated. About 90 percent of all cellular structures are, at least in part, glycoproteins, including all cell receptors, immunoglobulins, hormones, enzymes, and collagen, to name just a few.

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Immune Theory of Aging. A theory more appealing to me is the immune theory of aging. The immune system is how we defend ourselves against attack by any foreign aggressor that enters our body. It’s an amazingly good defense system and it uses several different weapons. White blood cells can overpower and gobble up attackers like bacteria and viruses. Other specialized white cells produce antibodies which circulate in the blood where they search out foreign invaders, overcome them, and make snacks out of them for our other cells to gobble.

The immune theory of aging is based on two main ideas. First, with age, our immune system's ability to produce antibodies declines. Second, our aging immune system may mistakenly produce antibodies that will damage our normal body proteins.

Ideally our immune system should make antibodies only to attack foreign proteins, or other chemicals, that are introduced from outside. Antibodies that mistakenly attack our own proteins may damage or even destroy our vital cells or proteins. This results in what are called autoimmune diseases, and not all of them are limited to older people.

When scientists first started talking and writing about this, way back around the turn of the century, it scared everyone. They named it "horror autotoxicus." It scared people because it pointed out the possibility that a person’s own immune system could become a personal poison. Your own immune system can kill you by making antibodies against your own cells.

This idea, scary as it is, is apparently true.

Those who think that a faulty immune system is the cause of aging argue that we’re certainly very likely to contact the diseases and pathologies of old age if our immune system stops defending us and begins producing antibodies that attack our healthy cells. For example, a young and healthy immune system might keep cancer in check, but it might not be able to do this later in life when it begins to function poorly. The thymus gland, you’ll recall, is in the upper part of your chest, and it produces some very essential components of the immune system, called T cells.

These white blood cells are absolutely necessary. Without them, your body can no longer fight off disease. Adherents of this theory tell us, that as soon as the thymus begins to wither after adolescence, it’s the beginning of the end. This withering of the thymus perhaps triggers the breakdown of physis - a notion in striking accord with Hippocrates.

Perhaps this theory sounds the best of all those discussed so far, but this theory, also, has its several flaws.

  • First of all, it’s not universal. Some animals that age well don’t have a well-developed immune system. Thus one of our requirements for a tenable aging theory isn’t met. Should we perhaps refine it in some way?

  • Secondly, the most likely indication of immune dysfunction with age is greater incidence of disease. But disease is pathological, not normal; and it hasn’t been shown to influence the normal aging process. This issue also perhaps deserves more careful thought.

  • Additionally, the immune system is subject to control by several hormones and by the nervous system, so there could be more basic sources for the changes found in it as we age. In other words, the decline of your immune system may be the result, rather than the cause, of aging.

  • And, it’s also possible that the development of autoimmune diseases could be caused by changes in the chemical structure (shape) of various protein molecules as we age rather than by our immune system’s mistakes. If so, the production of antibodies against them is an unfortunate, but not dysfunctional, response.

I’m inclined, after noting these objections, to dismiss most of them.

Here’s why.

First of all, let’s note that the immune system is incredibly complex, and, in spite of many recent breakthroughs, it’s not yet well understood. As noted earlier, it’s very difficult to distinguish cause from effect in such a complex arena. All biological systems are interrelated in complex ways and they’re all affected by aging. While, so far, no one system has shown itself to be the trigger of the aging process, the immune system remains, for me, a major focus.

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4. Theories of Aging: Why we age

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Telomeres. As you’ll recall, in the language of genetics, the sequence TTAGGG spells "the end." This sequence of nucleotides, repeated thousands of times, forms a protective cap - the telomere - at each end of each chromosome. Telomeres grow shorter with each division of a cell. Until they’re gone. The cell can then no longer divide and so ages and dies. Children with progeria, for example, age rapidly and die early because their telomeres grow shorter more rapidly than normal with each division of their cells. So telomeres have something important to do with aging. But telomeres alone cannot tell the whole story of why we age.

Longevity. In vitro cells ("in vitro" means "in glassware") - cells growing in laboratory cultures like those of Carrel or Hayflick (1996), eventually run short of telomeres and die. In vivo cells ("in vivo" means "in the living organism") - cells growing in living animals, do not. Animals and humans that die of old age do so well before they run short of telomeres. This observation suggests that some other genetic factor may be responsible for aging. If so, a reasonable approach is to compare animals and look for some common biological factor that accounts for their different life spans.

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Body as Brain. Receptors on some somatic (body) cells, for example, enable them to recognize and react to chemical factors, such as neurotransmitters, that mediate emotions and moods - rage, fear, joy, lust, love, grief, and gluttony, to name but a few. These ground our lapses into reason in ways often beyond awareness or comprehension. All cells are, in this sense, part of a network and send messages between each other much as we today send electronic mail between computers (cells) over the Internet (network). Because functions in such a network are distributed, distinctions between body and mind are more likely to mislead than to inform us.

Cell Differentiation. Distinctions between types of cells are more to the point. What differentiates a nerve cell from a skin cell? The repertoire of sugars displayed on the surface of a cell's membrane changes as it develops, differentiates, or sickens - a fact of obvious importance not only to the development of an embryo, but also to the maintenance and restoration of health.

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Sticky, Tasty, Sugarcoated Bubbles. It’s also obvious that, to form tissues, cells must be able to find others of their kind and adhere to them. That is, they must be able to sense each other and cling together. Here too, their sugary coats play an important role by endowing them with exquisitely precise and specific senses that we might just as well call cellular taste and olfaction (smell). These "cellular senses" are those that allow similar cells to stick together each other (but not to other kinds) by endowing them with, so to speak, coats of custom Velcro - sticky, tasty, sugarcoated bubbles.

Icky Stuff. Ahhh! But here’s another rub. Sticky, tasty things can be found not only by the good things, such as friendly neighbor cells or message molecules from friendly cells farther away; but, also, by the bad things such as toxins, viruses, bacteria, and other icky stuff. Let’s look now at how this happens.

Find and Bind. Insight into these infectious processes came with the discovery of lectins - a class of proteins that combines with sugars rapidly, selectively, and reversibly. Just the properties needed by an invader! Much repeated research has shown that bacteria use lectins on their surfaces to find and bind to sugars on their hosts. Strong evidence now supports the hypothesis that this find-and-bind process initiates infection.

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5. Anti-aging: Valid therapies

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Chemicals. I’d like to take a few minutes to warn against over-simplifying. You’ve all heard the super environmentalists who blame everything on "chemicals." Take us back to the zero-risk days of yesteryear when chemicals did not break-in or steal. (How’s that for a mixed but useful metaphor.) But there never WAS, nor can there ever be, a zero-risk world, free of chemicals. The world around us is a seething mass of chemicals and always has been. People and all living things consist of chemicals, and the oceans and continents around us, and the air above us. Every material thing consists of chemicals. Our gorgeous green plants of the earth belch more than four hundred billion pounds of complex organic chemicals into our air every year, most of which - in the wrong amounts or concentrations - are hazardous to people.

Poison Plants. The very freshest fruits and vegetables, grown using only the most natural of fertilizers, are filled with an astonishing array of chemicals - ketones, esters, lactones, acids, amines, amino acids, alcohols, mercaptans, terpenes, ions. And, again, most of them, in the wrong concentrations or amounts, are hazardous to people. A plant can’t move, and so must mount some sort of chemical defense against creatures that munch on it. So the plant makes its own chemical insecticides to protect itself. The chemicals that plants make are intended to be hazardous to creatures of meat who munch on plants - that’s insects - and that’s us too, folks. So even before overpopulation and before man began mucking about with the environment, the world was a dangerous place for us. And after we pile on this the monumental pollution we’re creating these days, we find ourselves in an increasingly noxious mess.

Polluted Water. Polluted rivers and sewers now provide water to drink and irrigate crops. Laws against DDT slam the barn door after the horse has gone. DDT has staying power. It’s been banned for decades now, but there’s still plenty of it in left in our rivers. It sometimes seems that no matter what we do, it just adds to our problems. When we ingest a new miracle antibiotic to kill dangerous bacteria, we eventually urinate the weakened antibiotic into the sewer system where the bacteria slowly and comfortably form immunities to it until the once-miracle-killer of bacteria becomes yummy food no longer a threat to the thriving bacteria. The water we drink, the foods we eat, the air we breathe are packed with dangerous toxins both old and new. If ever we needed an immune-system booster, it’s now more than ever before.

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6. Anti-aging: Future promise

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Introduction. We’ve talked about caloric restriction to extend life and examined several strategies - vitamins, antioxidants, glyconutrients, hormones, exercise, rest, stress reduction - to retard and, in some cases, even reverse the damage caused by free radicals as we age. But there’s more to aging than damage. And more to anti-aging than mere damage control. We can do better than this. Far better. Damage control and life-extension are temporary strategies that allow us to live until the more powerful strategies I’m about to discuss below become available over the next few years.

Advances. Significant advances in medicine, public sanitation, and personal hygiene have made major conquests of external pathogens over the past hundred years. This approach, important as it is, can only go so far. To sustain progress, to leap ahead, we must reach a deeper, more sophisticated level of biological understanding and control. Perhaps we can replicate cells to regenerate damaged organs - livers, nerves, hearts. Such experimental therapies are now beginning experimental trials. Thus, the future of medicine and the quest to end old age go hand in hand.

Breakthroughs. Scientific breakthroughs are now being made at a breathtaking pace that will increase the human life span to more than 150 years within a few decades. Any alert layperson now sees daily reports regarding germ cells, cloning, gene therapy, nanosurgery, stem cells, long-living worms, the human genome. Many of these reports are alarming, distorted, inaccurate, confusing, misleading, garbled, or, in some cases, just plain incomprehensible. I hope here to make clear what these reports mean to you, starting with germ cells.

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Cell Communication Failure. Aging results as protein synthesis declines and cells no longer respond correctly to cues from other cells. Or no longer send correct cues to their neighbors. Or both. Aging, in this view, is a cell communication failure that results from shortened telomeres. And here’s how it works.

The Aging Process. Cells, as they age, produce more and more free radicals that progressively cripple them and damage their neighbors. As tissues and organs thus decline, the organism that houses them ages. Then dies. This is death’s language. We’ve had enough of it. Now let’s learn the language of life.

Life’s Language. The language of life is the language of signals and receptors that cells use to communicate with each other. Its four-letter alphabet is coded in your DNA. Its words are the proteins coded by your genes. The set of DNA specifications for building a living thing is not, however, like a collection of engineering drawings.

Embryonic Algorithm. It’s more like what a computer scientist would call an algorithm or we would call a recipe. More precisely, your DNA is rather more like an integrated set of software (genome) with many programs (genes) that work together like a set of recipes specify the ingredients and steps needed to prepare a meal - the feast of your life! Your genome describes the steps that direct your embryonic cells as they divide into progressively more differentiated cells that unfold to become you.

Unfolding You. As an embryo unfolds from the union of sperm with egg, its telomeric clocks begin to tick. And with each click, the telomeric hoods of each cell retract to reveal the next steps to take to become a different type of cell. This is the essence of embryogenesis. It also tells each new type of cell where to go (what gradients of scents to follow like some bloodhound) to form the unfolding embryo. This is the essence of morphogenesis - the unfolding of you.

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Signals and Receptors. And the language of life that makes this miracle possible is the familiar language of signals and receptors we’ve been discussing all along, which I hope and trust you’re finally becoming more comfortable with.

Growth Factors. As you know, the language of signals (messenger molecules like hormones) and receptors (often glycoproteins of the glycocalyx on the surface of a cell) is the language by which enzymes, hormones, or growth factors for example signal a cell to tell it when to divide, or to make different stuff, or simply to do something else.

Rosetta Stone. A development that may offer a Rosetta stone to help us further decipher this language comes from research at Human Genome Sciences of Rockville in Maryland. Its chairman and chief executive officer, Doctor William A. Haseltine, has said that the company has isolated more than 75 percent of all human genes in full-length form.

Critical Genes. From them, Haseltine says, 14,387 genes that code for signals or receptors have been isolated by a computer search for the DNA sequence common to all such cell signals and receptors.

Life’s Vocabulary. We now know life’s vocabulary. These fourteen-thousand-and-some-odd glycoproteins are its verbs. These genes comprise life’s language: the signals and receptors that enable cell-to-cell communication.

Immortality. This is the language of life. And of immortality.

Eighty-four More. Most of the growth factors involved in embryonic development are likely to be included in this set. These are the ones that, once identified, will allow us to use stem cells to generate any of the 254 types of human tissue now known. And, of about eighty-four more, yet to be discovered.

Cell Charts. Biologists now have the beginnings of a technique that can be used to chart biological cells in much the same way that the periodic table of chemical elements has long been used by physicists and chemists to chart chemical elements.

Regenerative Medicine. This is a breakthrough. A real breakthrough! We’ve now crossed the threshold of a new era - the era of credible theoretical biology and regenerative medicine. Regenerative medicine, a term coined by Haseltine to describe the renewal of body tissues with natural signals that control their growth, "should permit us to maintain our bodies in normal function, perhaps perpetually," he says.

Controlled Growth. Control is the operative term here. Uncontrolled growth of immortal cells that go wherever they want and proliferate wildly describes cancer. Presumably, many of the factors that guide the development of cells and keep them under control will also be found among these first 14,387 genes.

Human Genome Sciences. Human Genome Sciences has filed patent applications on the genes it has discovered. So far, the company has been granted patents on 652 of these vital and crucial genes.

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Conclusion. We live in a world of stunning complexity that no one fully understands. Atoms join, forming molecules. Molecules of all varieties jiggle and dance to somehow assemble themselves into living cells. Cells interact to form organisms - plants and animals, ants and aardvarks, worms and us - which, in turn, form ecosystems, economies, societies.

Biology offers us the theory of natural selection, on one hand, to explain how this majestic order comes about - by Chance. Physics offers us entropy, on the other hand, to explain how it all just as constantly falls apart - by Necessity. Anyone who views the stars, or cradles a child, is awed by the magnificent design - this incredible balance of Order and Chaos - that we observe in the world.

The interplay of Chance and Necessity are apparently more subtle than many imagine.

We’ve explored here what some are calling the new science of anti-aging. Summing up now, I sincerely hope to leave with you with an informed understanding of its message - a message, good beyond our wildest dreams, that touches your sense of the sacred.

Click here to order a copy of my anti-aging book from the American Nutrceutical Association.

(205-980-5710).


Future topics on this web site will deal with the safety, efficacy, and glycobiology of glycoproteins. I plan to investigate the effects of such supplements on pregnancy, embryology, childbirth, children, exercise, and the immune system as well as study their effects on a wide variety of maladies including aging, immune system dysfunction, and chronic disease.

Visit Us Often. Visit us often and we’ll keep you posted as the news comes in!

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Copyright © 1999 Darryl M. See All rights reserved.