The Four Dimensions of Aging

Age Right
by Karlis Ullis, M.D., Greg Ptacek

(Page 2 of 2)

When I first met Jackie Joyner-Kersee, she was an eighteen-year-old freshman who had come to UCLA to play basketball. After establishing that she could do that exceedingly well, she decided to test her talents in track and field. In an amazingly short time she was competing in the most difficult endeavor, the heptathlon, comprised of seven different events: sprinting, distance running, shotput, javelin, high jump, hurdles, and long jump. In the 1984 Olympic Games she took the silver medal in pentathlon, barely missing the gold by a few points. In the 1988 and 1992 Olympic Games, she took home the gold. Her domination in this event, with multiple world records over such a long period, has never been equaled.

With her record of achievements you would never know that Jackie has an illness that can be devastating to an athlete: asthma. By the time I met Jackie, I had already begun to formulate a theory about aging after a long and intensive study. I had concluded that all the various processes of aging in the human body could be explained by changes that occur in three broad categories. Working with Jackie caused me to rethink the theory and add a fourth category. We therefore have these four categories:

1. Neuroendocrine: how hormones and the nervous system signals interrelate

2. Energy Metabolism: how we gain and utilize energy, or the effectiveness of our energy metabolism system

3. Biomechanical: how we move

4. Lifestyle and Environment: the social and personal dynamics that govern our personality and style, and how we relate to one another, the world, and the environment.

Another person with an illness like Jackie's might have dismissed the idea of becoming a competitive athlete. Make no mistake, there were a number of times when her asthma was so severe that it required emergency treatment. But Jackie adapted to her environment and chose to succeed despite the pain and adversity.

There is actually another dimension of aging — genes. Your biological parents affect the way you age. But there is little you can do about this dimension of aging, so there is really no practical reason to discuss it. In the next ten to twenty years this fifth dimension of aging will become increasingly important. The Human Genome Project, the international scientific effort to map all 100,000 human genes, is ahead of schedule and has already yielded new therapies for a wide range of diseases associated with aging and others — from breast, prostate, and lung cancer to inserting longevity genes or repairing injured genes to give you an extra thirty or more years of good living beyond your normal life expectancy. Soon many of the diseases and afflictions associated with our advanced years for — example, Alzheimer's and osteoporosis — might be cured by fixing a cell's suboptimal genetic structure. In the meantime, our best strategy is to halt and even reverse the effect of aging by taking full advantage of the antiaging breakthroughs that are imminent.

All of us are dealt a genetic hand with certain physiological advantages and disadvantages. Even with the best training, you may never be capable of winning an Olympic heptathlon or decathlon. But you are capable of reaching your maximum vitality with an integrated anabolic program that addresses the four dimensions of aging.

Each of us is a synergistic biological entity composed of interrelated systems. All these systems age in a different way and for different reasons. And they all affect one another and overlap in unexpected ways. While addressing each is vital for an effective antiaging program, the four major causes of aging are listed in order of their relative importance.

Dimension of Aging #1: Neuroendocrine

There are two parts of the neuroendocrine system. The "endocrine" part refers to the hormones (discussed in detail in the last chapter). The "neuro" part refers to "neurotransmitters," a term coined in 1904 to describe chemical compounds stored in nerve cells of the brain and other organs. When stimulated, these chemicals cross the gaps between nerve fibers, transmitting messages within the brain and to other parts of the body.

Neurotransmitters and hormones are closely linked: the former controls the release of the latter. Too much or too little of a neurotransmitter can throw the delicate balance between the hormones into disarray.

As we age, we produce less of many hormones, including the sex hormones, DHEA, growth hormone, thyroid hormone, melatonin, as well as neurotransmitters, including dopamine, acetylcholine, and norepinephrine. Compounding the problem is the decline — both in number and sensitivity — of the receptors in cells that receive the hormones. Even if you have enough of a hormone, the target cells become insensitive to hormone stimulation.

This relationship between neurotransmitters, hormones, and cell receptors is responsible for human behavior, from emotional moods (such as anger or pleasure) to physical feelings (hunger or pain), and movement (arms and legs), involuntary processes (digestion, breathing), and cognitive abilities (intellectual understanding, memory).

Neurotransmitters

There have been more than one hundred neurotransmitters identified, but many of them fall into three broad categories: acetylcholine, dopamine, and serotonin.

ACETYLCHOLINE: Acetylcholine is distributed throughout the body, but in the brain it is involved in the human mind, the mental functions that differentiate us from other mammals. These functions include insight, critical judgment (also called executive function), memory, language, spatial relationships, sensory impressions and interpretations, speech, and thought. Aging leads to declines of the enzyme called choline acetyl-transferase that controls the biosynthesis of acetylcholine from choline and acetyl-coenzyme A.

Full-blown depletion of acetylcholine results in Alzheimer's disease. Alzheimer's is not a normal consequence of aging. Some of us will have some degree of impairment of memory, language, thought, orientation, and critical thinking if we live long enough. This is, however, distinct from Alzheimer's, a very specific disease process seen in older people but not a condition present just because you are older or aging.

While Alzheimer's is thought to have a significant genetic mechanism associated with it, a number of risk factors increase your likelihood of getting it. They range from trauma to the head (also called boxer's dementia) to couch potato syndrome. Regarding the latter, there is a statistical correlation between a higher level of education and/or a lifetime of ongoing adult intellectual stimulation and the decreased risk of Alzheimer's.

DOPAMINE: This category includes, in addition to dopamine, norepinephrine, and epinephrine, which are related to energy release and consumption. These keep us vigilant and alert, controlling the release of adrenaline for the "fight or flight" mechanism that automatically arouses us in an emergency. When stimulated, dopamine makes your heart beat faster, increases your rate of breathing, and generally makes you ready to do battle, flee for your life, or make passionate love. It is also responsible for involuntary movements (such as blinking), emotional drive, and spontaneity.

Dopamine declines with age, but you can also burn it out earlier by taking cocaine, crack, speed, or other stimulants. The "high" from these "uppers" comes from the quick acceleration of dopamine, which is typically followed by an emotional letdown as the body's supply of dopamine is depleted.

Norepinephrine, was at the heart of the revolution in biochemical treatment of depression. Depressed patients, it was discovered, have low levels of norepinephrine, and many antidepressant medications increase the concentration of norepinephrine in the brain.

The majority of the 10 million or so dopamine and related cells are located deep in the brain. As dopamine is used, a very toxic free radical is produced that contributes to the demise of its parent cell, the dopamine neuron. With aging, this activity increases to the point where there are not enough dopamine neurons left to do their important function since new ones aren't being generated. Research on stimulating the growth of new dopamine cells and the creation of additional dopamine is currently in progress.

Dopamine's self-destructive nature can be accelerated by certain medications (such as L-dopa), environmental toxins (exposure to heavy metals), or even lifestyle choices (a pro-oxidative diet and drug abuse). Full-blown dopamine deficiency is known as Parkinson's disease. You have to lose about 75 percent of your dopamine neurons before you have a case of obvious Parkinson's.

A dramatic story about lifestyle-induced destruction of the dopamine neurons concerns a chemical compound called MPTP and a mystery involving two graduate students living on opposite ends of the country: Santa Cruz, California, and Stony Brook, New York. Both students had a nasty little habit — heroin — that they didn't mind sharing with friends for the right price. Coincidentally, they both made the same mistake at about the same time while synthesizing the drug in their illicit labs. They inadvertently created MPTP (1-methyl-4-phenyl-1,2,3,6-tetralydropyridine), which turned out to be extremely toxic to the dopamine neurons. Weeks after using these heroin batches, young addicts were coming to medical facilities on both coasts and presenting the symptoms of classic Parkinson's disease, normally seen in the elderly.

Some scientists are predicting a new wave of Parkinson's as the result of people using cocaine, crack, and other stimulants combined with other pro-oxidants such as smoking, drinking, antioxidant-poor diets, and poor sleep patterns. In this scenario all these factors combine to destroy the dopamine neurons, pushing them into an auto-destruct point of no return. The old wave of Parkinson's disease sufferers, who are now dying off, is thought to have been the result of exposure to industrial chemicals (before today's worker safety and pollution control regulations were instituted) and from a viral encephalitis epidemic that struck millions in the U.S.A. in the 1920s.

SEROTONIN: Serotonin influences appetite, cravings, and obsessive behaviors. A person with low serotonin can be impulsive, aggressive, violent, anxious, restless, and depressed (even suicidal), and exhibits compulsive habits including overeating and drug and alcohol abuse. Too much serotonin can lead to impaired sexual function, including an inability to have an orgasm or an ejaculation, as well as nausea and diarrhea. These are the same side effects associated with the popular drugs Prozac, Paxil, Zoloft, and the others known as SSRIs (Selective Serotonin Reuptake Inhibitors). These drugs block (inhibit) the nerve cell from reabsorbing serotonin once it is released, prolonging the action of the serotonin. Stressed-out people take SSRIs because serotonin, known as the civilizing neurotransmitter, promotes tranquillity and decreases mental activity.

Pregnancy is an excellent example of serotonin dominating the other neurotransmitters. The "glow" that pregnant women exhibit is largely due to their increased levels of serotonin. This is a time when serotonin overrides the effects of norepinephrine, which is excitatory. To preserve the fetus, women sleep more, gain weight, and lower their rate of mental activity. Because of lowered mental activity, there is less pain perception and an increased pain threshold, vital, as your mother can tell you, during birth.

Melatonin is made from serotonin in a two-step process in the pineal gland of the brain. The pineal gland, also called the "seat of the soul" by the ancient Greeks, primarily functions to produce melatonin, which operates as your body's "biological clock." Melatonin production and release is governed mainly by cycles of light and dark (night and day and seasonal) — turned off by daylight and turned on by darkness. The pineal gland and melatonin also regulate the daily rhythmic action of the hypothalamus-pituitary gland cyclical activities. This regulation is the reason for night and day differences and fluctuations in the secretion of growth hormone, testosterone, cortisol, and other hormones.

Serotonin is made in our brain cells during the day as we eat carbohydrates, then gets rapidly converted to melatonin starting at sundown. Melatonin's peak level release is at about 3:00 A.M. Since melatonin affects the main endocrine center of the brain (hypothalamus-pituitary), it influences a wide range of functions from immunity to fertility, growth, and insulin production. We don't feel the effects of a low level of melatonin as directly as those of serotonin. The effects are subtle and spread out over the twenty-four hours of a day. A big shot of serotonin affects you immediately. A large enough dose of melatonin can do the same, but that is not the way our bodies normally function.

Unlike the other two major neurotransmitter groups, serotonin does not decline dramatically over time (although melatonin secretion decreases sharply with age). But because the others do, this creates a greater dominance of serotonin over melatonin, acetylcholine, and catecholamines. Some scientists theorize this imbalance may be a major cause of aging. If you are less than sixty years old and have a serotonin-melatonin imbalance, you will exhibit signs of accelerated aging, including increased stress and cortisol levels, resulting in depression, anxiety, poor sleep, impaired glucose metabolism, and sexual dysfunctions; and/or poor impulse control, leading to behaviors such as drinking, overeating, recklessness, aggressiveness, and violent tendencies.

Dimension of Aging #2: Energy Metabolism

There are two components to the energy metabolism system. The first is the delivery of fuel inside the cell, that is, the process of getting food from your mouth into the cell. The second is getting fuel into the mitochondria, the cells' power plants which produce the high-energy compounds that cells and muscles need to function.

You derive the maximum and most efficient energy from glucose-based fuel sources. If exercise is prolonged and strenuous, then fat products called fatty acids and amino acids are burned (oxidized) for fuel instead of glucose. An efficiently working metabolic system obtains energy first from glucose/glycogen, and when it has exhausted that fuel, then from fats and proteins.

With age, both of these metabolic functions begin to fall apart. It becomes increasingly difficult to move glucose into the cell, and the mitochondria begin to wear down and work less efficiently.

A primary culprit in this aging process is insulin. A vital anabolic hormone, in excess it becomes dangerous. Normally, insulin serves as the equivalent of a freight train, transporting glucose to the cell. For a number of reasons, however, cells become resistant to insulin with age, essentially preventing it from doing its job. Cut off from its regular fuel supply of glucose, cells have no other choice but to start burning the furniture to keep the furnaces running, that is, the fatty acids from fat stores.

Sounds great, doesn't it? As we get older, we burn less glucose and more fat. What could be wrong with that? Well, back at the train station, the insulin workers are getting itchy. Blocked from doing their glucose-transporting job, the insulin agents begin storing everything you eat as fat. Even though your cells are burning fat instead of glucose, insulin is working even harder to store it, and the net result is that your body fat increases.

The second bit of bad news about insulin is that with age it fails to give the proper signals for the synthesis of proteins (the muscle's building blocks). As a result, you lose muscle mass, which of course worsens the first problem of increasing body fat. If you think this sounds like a formula for middle-age flab, you're right.

The third piece of bad news about insulin is that with age the bloodstream is flooded with excess insulin and glucose. Instead of working together in a productive relationship, insulin and glucose now shun each other and linger in the blood, causing trouble for blood vessels and vital organs such as the eyes, nerves, and kidneys. (The worst-case scenario of the glucose-insulin system breakdown occurs in a condition known as Metabolic Syndrome X and further down the road, diabetes.

Excess insulin isn't entirely responsible for the energy-metabolism problems that occur with aging. The mitochondria wear down and begin leaking the equivalent of smoke fumes. Imagine two power plants that produce electrical energy from burning gasoline. One is an efficient engine that burns the fuel cleanly with little smoke. The other engine burns the gasoline but produces a lot of smoke and soot, polluting itself and the neighboring area. The already damaged engine damages itself more as it converts one energy source to another. This is what happens with aging and oxidative damage to the mitochondria. The "smoke fumes" in this case are called free radicals, which are the basis for a leading theory of why we age.

Many neurodegenerative diseases such as Alzheimer's, Parkinson's, diabetes, and stress-induced memory damage are the result of the body's energy system failing either at the cell insulin-glucose transport level or at the intracellular level involving the mitochondrial power plants.

Dimension of Aging #3: Biomechanical

This is the system of pumps (heart), pipes (blood vessels), levers (joints), pistons and springs (muscles and tendons), and framing (skeleton, bones). Built for motion, this system deteriorates when not used. A good example of this would be if you stayed in bed for a week. Upon arising, you would experience a quick dose of aging symptoms: stiff joints, weak muscles, shortness of breath, and, if you were tested, a loss of bone mass. Interestingly, astronauts in space experience the same symptoms because of the lack of gravity.

Underutilizing your biomechanical system can have devastating direct and indirect consequences. An intrinsic problem is the stagnation or pooling of body fluids. When fluids are not circulated, they get dirty, like a pond that has no runoff versus a fast-running stream. The stagnation of body fluids makes it easier for bacteria or other invaders such as viruses to camp out in our bodies. Inactivity can also lead to curvature of the spine, brittle bones, creaky joints, and weak muscles, which can increase the risk of falls and injuries.

Dimension of Aging #4: Our Lifestyle Choices

Lifestyle choices play an enormous role in our quality of life as we age. We didn't have a choice of who our parents were. We were not given a choice about the culture we were born into, its values, beliefs, and expectations. The genes and the culture we acquire have a powerful impact on our health, aging, and longevity. In the United States, for example, persons of lower economic status and education have shorter life spans. People whose religion forbids alcohol, caffeine, and smoking (Mormons and Seventh-Day Adventists, for example) have a greater chance for a longer life.

But longevity per se is not the goal of this book. It is not how long you live that ultimately counts but how well you live. Habits, social contacts, family and loved ones, even one's outlook on life play a scientifically verifiable role in the health of everyone, especially as we age. Exercise, diet, and appropriate supplements can modify the genetic hand we were dealt. I will show you how, beginning with the next chapter.

Copyright © 1999 by Dr. Karlis Ullis, Greg Ptacek

About the Author

Karlis Ullis, M.D., is a sports medicine and rehabilitation physician at UCLA and has served as a physician at five Olympic games. His antiaging program has been featured on the Today show, Hard Copy, Dateline NBC, and Sally Jessy Raphaël. He serves as the medical director of the Sports Medicine and Anti-Aging Medical Group in Santa Monica, California (www.agingprevent.com). Dr. Ullis is also the author of Super "T": The Complete Guide to Creating an Effective, Safe, and Natural Testosterone Enhancement Program for Men and Women.

Has written articles for many leading health publication, including Longevity and Men's Fitness. He lives in Los Angeles, California.