Brian Klepper 

How do you live a long life? Take a two-mile walk every morning before breakfast.

Harry Truman
33rd US President, who lived to 88

DAWN, n. The time when men of reason go to bed. Certain old men prefer to rise at about that time, taking a cold bath and a long walk with an empty stomach, and otherwise mortifying the flesh. They then point with pride to these practices as the cause of their sturdy health and ripe years, the truth being that they are hearty and old, not because of their habits, but in spite of them. The reason we find only robust persons doing this thing is that it has killed all the others who have tried it.

Ambrose Bierce, The Devil's Dictionary 

I started taking long walks with my close friend Bob thirty-five years ago when we were students in Holland. We would walk and discuss the things that young people ponder, passing time in the brisk beautiful outdoor landscape of Northern Europe. We always maintained a quick pace, but never minded the effort, because the activity was filled with ideas and always-inviting scenery.

When I returned home, walking was a habit that stuck with me. When Bob and I lived in the same town, we'd get together regularly to walk the dogs. On my own, I found that I could go out for a stroll and think, chewing on whatever I was working on and, getting a little distance from it, find perspective. Elaine and I still walk, constantly, and that's where we get some of our best talking in. Walking has been respite from the rush, a place to hash out conflicts or work out plans, a way to meditate and regain balance.

When I left my post at the University of Florida about 20 years ago and returned home, I traded a landlocked town for the coast. As quickly as I could, I resettled within a few blocks of the beach in a small community on an island off Jacksonville, in Northeast Florida. Then, as now, I was literally within a five minute walk of a 300 foot wide, hard-packed, sugary white sand beach on the Atlantic, stretching for miles both north and south. In addition to the spectacular, always changing beauty of a vibrant seascape - birds, dolphins, turtle nests, fish and other sealife; the boats and ships just offshore; the surf rolling in and lapping the beach - it was perfect terrain for a habitual walker.

Even so, as easily accessible as it is, and though I know lots of people long for just this sort of environment, there have been periods when I lost my discipline, when I took the opportunity for granted and somehow just didn't get around to it.

Then came the moment 5 years ago when I unexpectedly had open heart surgery, a 5 vessel CABG, the result of lousy genes and the gradual relentless buildup of plaque choking off my blood vessels. During the procedure they collapsed and then re-inflated my lungs, and I knew it would take work to ameliorate my shortness of breath. I started walking again immediately, through the halls, on the second day in the hospital following my surgery, and by the time I left 3 days later I was up to walking more than a mile a day.

I continued when I returned home and worked through recovery, and though increasing my distance went slowly, I kept at it. During a follow-up with my surgeon, he commented, "The best thing you can become is a walking fool. It's low impact, steady and its good for you in all kinds of ways, especially with what you're up against."

And then, again, time passed and I got comfortable and distracted. I skipped my walks and then they trickled away, until I was just walking weekends again. I told myself that I was really in OK shape, but the truth was that I put on weight and that I had slipped into a malaise.

Recently, I had a discussion with a good friend, a preventive cardiologist, who gave it to me straight. I had shared the numbers from my last blood panel. "Look," he said, "you're not taking this seriously. Unless you get your LDLs (the bad cholesterol) down below 60,  you're going to continue laying down plaque, and the risk increases. If you're interested in doing what you can do, you need to get religion on this. Get lean. Eat carefully and ramp up your exercise."

And so I have.

This isn't just theory. Below is a picture from the REVERSAL Trial, led by Steven Nissen MD, chief of Cardiology at Cleveland Clinic. It clearly shows the before and after effects of managing LDL to below 60. After 18 months of the reduced LDLs, there's been a significant opening of the vessel. This is what I'm shooting for.

So we've cut out most breads and sweets. Cookies are out. Our diet is mostly fruits, veggies and fish. Once you get your head around it, it makes sense and you gradually lose the longing for the comfort foods: a milk shake, macaroni and cheese, or a fried fish sandwich.

And then there's the walking. It's a flat 3 miles, 50 minutes door-to-door, down to the lifeguard station on the beach and back, walking fast. Right now, in the NE Florida swelter, I'm soaked through when I return. I do this twice a day. On my suburban beach, around 6AM, there are 200 people out there walking before work. After work, you see  a lot of them again.

 An embarrassing quantity of pounds has melted off. I'm becoming leaner and stronger than I've been in years. The next blood panel will tell. When I'm tempted by some forbidden food, I think of 60 and my will to shrink the plaque that's strangling my vessels.

And I walk.

We were watching tonight a great program on PBS about Billie Jean King and her wonderful tennis career. Her 1973 match, or dare I say grudge match, against Bobby Riggs, was a delight to the eyes and the soul. We relished her strategy of running ragged this aging fool from one end of the court to the other. There she was: a skilled, rebellious young woman facing a male chauvinist who taunted her to test her mettle against his. But the match had a much larger meaning; it was emblematic of the new generation, of a new world upending the old order and its tired prejudices, not in a bloody revolution fought in the streets—but in a fair, civilized match on the tennis court. How many of you remember a single feminist demonstration? but we all remember this historic match; such was its impact.

However riveting her life story was, what caught my attention was her secret weapon: her tremendous ability to focus, to remain calm under pressure, in fact to relish stressful situations. As she herself said, minutes before a match all her anxieties and insecurities would be replaced by determined calm and focused planning. How could she do that?

It’s all in your head

The neurons in our brain talk to each other through chemicals that are called neurotransmitters. One of those is called dopamine, and its function is invaluable; when we have a pleasurable experience of any kind, dopamine is released. We thus learn to associate this experience with reward and pleasure and tend to repeat it. This is important to our brain’s unconscious decision- making. Just think of it: if on every occasion that we encountered a delicious meal, or a glass of wine, or making love, we had to gingerly try it first to see if we liked it—we would be paralyzed with indecision. Billie Jean King did not have to convince herself that she loved the game every time she stepped on the court—her brain had already made this decision for her.

What happens when dopamine levels in the blood are elevated?

The physiological and psychological effects of elevated dopamine are wonderful: a sense of optimism, exhilaration, even euphoria; a sense of increased energy that can escalate to hyperactivity, sleeplessness, loss of appetite, increased heart rate and hyperventilation. As part of this behavioral complex, there are a few other traits: extremely focused attention, motivation and goal-directed behavior. Do you recognize these as ‘symptoms’ of falling in love? Can the pounding heart be the reason for the association of love with the heart? Can it explain the rapt attention of the young lover earnestly listening to her mate’s nonsense?

What about Billie Jean’s uncanny ability to focus on the game? She loved the game, she was in love with it. And I’d bet her dopamine levels were sky high as well.

It is a cliché that love made the world go round. Unfortunately, my friend, I hate to disillusion you—it’s all in the dopamine.

Dov Michaeli MD, Ph.D

I was really amused by Dr. Pat Salber’s latest posting on hapless guys gone shopping.  Was this a subtle literary allusion to Damon Runion’s “On guys and dolls”? His ‘guys’ are pretty much the same: a bunch of pathetic, testosterone-exuding losers. Even more amusing was the storm of plaintive protests from our guy readers, who claimed that this was a stereotype that was divorced from modern reality.

Seriously, how did stereotypes come to be accepted? If they did not have some roots in reality, Darwinian theory predicts that they would not survive the selective force of public acceptance. If you think that the “dumb blonde” or the “stupid jock” stereotypes have no basis in reality—think again.

Evolutionary Psychology.

Broadly speaking, this field is attempting to explain human behavior in evolutionary terms, or more specifically, in terms of survival advantage. The field is fraught with problems, the major one being that its analysis is by and large retrospective. What I mean by that is that the investigator describes a certain human behavior, and then in effect says “but of course, it makes a lot of evolutionary sense”, many times without a shred of empirical evidence, all the fruit of armchair “thought experiments”. An example: in 2001 a book was published by MIT Press (can it get more prestigious than that?) titled “A Natural History of Rape: Biological bases of Sexual Coercion”. In it the authors, Craig Palmer and Randy Thornhill, argue that rape should be expected because it increases the number of the rapist’s offspring; voilá, survival advantage—Q.E.D. Both authors are respected university researchers, but I submit that such a conclusion ignores overwhelming neurobiological evidence suggesting that far from doing what comes naturally, our rapist guy is actually deficient in his decision making power and his “executive functioning”—traits that reside in the prefrontal cortex of the brain.

Well, maybe not a very scientific “science”, but you’ve got to admit that it’s a lot of fun.

Seriously now.

One of my favorite evolutionary psychologists is Dr. Satoshi Kanawaza of the London School of economics, a truly creative researcher and thinker. To give you an idea why I like to read his papers, here is a selection of a few of them:

1. Kanazawa, Satoshi. 2007. "Beautiful Parents Have More Daughters: A Further Implication of the Generalized Trivers-Willard Hypothesis (gTWH)", Journal of Theoretical Biology. 244: 133-140

2. Takahashi, Chisato, Toshio Yamagishi, Shigehito Tanida, Toko Kiyonari, and Satoshi Kanazawa. 2006. "Attractiveness and Cooperation in Social Exchange", Evolutionary Psychology. 4: 315-329.

3. Kanazawa, Satoshi. 2006. "Why the Less Intelligent May Enjoy Television More than the More Intelligent", Journal of Cultural and Evolutionary Psychology. 4: 27-36.

4. Kanazawa, Satoshi. 2006."Violent Men Have More Sons: Further Evidence for the Generalized Trivers-Willard Hypothesis(gTWH)" Journal of Theoretical Biology. 239: 450-459

5.Kanazawa, Satoshi and Deanna L. Novak. 2005. "Human Sexual Dimorphism in Size May Be Triggered by Environmental Cues." Journal of Biosocial Science. 37: 657-665. What ‘size’ is he referring to?

6. Kanazawa, Satoshi. 2005. "Big and Tall Parents Have More Sons: Further Generalizations of the Trivers-Willard Hypothesis." Journal of Theoretical Biology. 235: 583-590

7. Kanazawa, Satoshi and Griet Vandermassen. 2005. "Engineers Have More Sons, Nurses Have More Daughters: An Evolutionary Psychological Extension of Baron-Cohen's Extreme Male Brain Theory of Autism and Its Empirical Implications

8. Yamagishi, Toshio, Shigehito Tanida, Rie Mashima, Eri Shimoma, and Satoshi Kanazawa. 2003. "You Can Judge a Book by Its Cover: Evidence that Cheaters May Look Different from Cooperators." Evolution and Human Behavior. 24: 290-301

9. Kanazawa, Satoshi and Rebecca L. Frerichs. 2001. "Why Single Men Might Abhor Foreign Cultures." Social Biology. 48: 321-328.

And so on, and so on.

If we apply some rudimentary logic to the titles, we would have to conclude that  big and tall men (paper 6) are violent  (paper 4) and they are also ugly, because if they were attractive they would have had more daughters (paper 1).

Since I had the fortune of having one son and one daughter I am in limbo (recently abolished by the Catholic Church, after several centuries of existence): I should be short, non-violent, and ugly. My wife wholeheartedly concurs. Saving grace, I don’t like to watch TV, which at least makes me intelligent (paper 3).

Back to the dumb blonde

A recent paper by Kanazawa and Jody L. Kovar of Indiana University of Pennsylvania ( "Why Beautiful People Are More Intelligent." Intelligence. 32: 227-243,2004.) illustrates the “thought experiments” used in many such publications. The authors suggest that:

1. Blondes are perceived in most cultures as more attractive,

2. Men prefer great looks over awesome intelligence (to wit, the irrefutable “evidence” that “gentlemen prefer blondes”).

It would then make perfect evolutionary and economic sense for blondes to invest their energy and talents in snagging an attractive, high earning man, rather than invest in their own education. All their daughters (paper 1) will be intelligent, attractive and… blonde.

Hence the stereotype. These gals are not dumb, they just didn’t go to school; they actually made a smart economic decision. Who would argue with such logic? Certainly not a dumb blonde.

In terms of my own situation, I am a total evolutionary failure. And you, Pat, are just too smart for your own evolutionary good.

Dov Michaeli MD, Ph.D

A few weeks ago, a fascinating story about the effect of the mind on physical well-being was widely published in the newspapers. A group of hotel room maids received a physical exam and were told that their work, making beds, cleaning baths, and vacuuming rooms is equivalent to daily moderate exercise and is good for their health and fitness. Another group of maids, in another hotel, received the physical exam only. Three weeks later, the maids who had been told that they were in good physical shape reported feeling in good health, had a low rate of absenteeism, and reduced their blood pressure from the initial exam. None of these were evident in the control group. Impressive, but hardly compelling. The usual criticisms of small groups, non-random selection, the short observation time—all these are real experimental issues, and “more studies are necessary” is the usual caveat following such experiments.

Enter the immune response.

During the last two decades sporadic reports were published in the scientific literature, claiming that both in animals and humans, state of mind had a significant effect on immunity. Stress in animals suppressed their immune response and increased their susceptibility to infection and cancer. Similar results were shown in humans, albeit under less controlled conditions.

Now comes a report in the April issue of the Journal of the American Geriatric Society, by Drs. Irwin and Holmsted of UCLA and Dr. Oxman of UCSD. They examined the effect of tai-chi on elderly people’s immunity to shingles, caused by a virus called varicella zoster.

The randomized, controlled clinical trial included 112 healthy adults ages 59 to 86 (average age of 70). Each person took part in a 16-week program of either Tai Chi or a health education program that provided 120 minutes of instruction weekly. Tai Chi combines aerobic activity, relaxation and meditation, which the researchers note have been reported to boost immune responses. The health education intervention involved classes about a variety of health-related topics.

After the 16-week Tai Chi and health education programs, with periodic blood tests to determine levels of VZV immunity, people in both groups received a single injection of VARIVAX, the chickenpox vaccine that was approved for use in the United States in 1995. Nine weeks later, the investigators did blood tests to assess each participant's level of VZV immunity, comparing it to immunity at the start of the study. All of the participants had had chickenpox earlier in life and so were already immune to that disease.

Tai Chi alone was found to increase participants' immunity to varicella as much as the vaccine typically produces in 30- to 40-year-old adults, and Tai Chi combined with the vaccine produced a significantly higher level of immunity, about a 40 percent increase, over that produced by the vaccine alone. The study further showed that the Tai Chi group's rate of increase in immunity over the course of the 25-week study was double that of the health education (control) group. The Tai Chi and health education groups' VZV immunity had been similar when the study began.

In addition, the Tai Chi group reported significant improvements in physical functioning, bodily pain, vitality and mental health. Both groups showed significant declines in the severity of depressive symptoms.

Is this study convincing?

The study was well-designed, well-controlled and carefully executed. It is the first study in humans that lends credibility to the notion that our immune response is controlled by the brain. This study is a harbinger of more serious studies, not only demonstrating the mind/body connection, but also the physiological mechanism by which this is accomplished.

Is the day when we could will ourselves to better health far off? How exciting!

Dov Michaeli MD, Ph.D

We all know the devastating statistics:

· 13.5 million people in the US suffer from coronary artery disease

· 8 million people have diabetes type 2.

· 95,000 people are diagnosed every year with colon cancer, and a sedentary lifestyle increases the likelihood of getting this disease by 40%.

· People who don’t exercise have about a 60% increase in osteoporosis; 250,000 suffer from hip fracture every year.

· 50 million suffer from hypertension.

· More than 60 million people in the US are overweight.

You might conclude from the last bullet that obesity is the culprit. You’d be only partly right. Lack of physical fitness is the other culprit, regardless of percentage of body fat. Even if we take people with a high % of body fat (more than 25%), the relative risk of death from all causes in the fit person is half that of the unfit.

Exercise and the body.

The effects of exercise on the body are well known:

· Exercise increases HDL, the good cholesterol, by an average of 4.6%. This, in turn, results in a decreased risk of coronary artery disease.

· Exercise increases insulin sensitivity, reducing the risk of metabolic syndrome and diabetes type 2.

· Exercise strengthens the heart muscle, improving its function.

· Exercise increases bone size and density, reducing bone loss due to aging and osteoporosis.

· Exercise increases muscle strength, coordination and reaction time. Result: improved balance and stability; reduction in falls and bone fractures.

What about mind?

This is a truly fascinating story, and you can read about it in more detail in an article in Newsweek, March 26, 2007 , by Michael Craig Miller, MD, from Harvard Medical School . Here are the salient points:

· Exercise has been known for many years to give, during and after exercise an “endorphin high”. This is the feeling of satisfaction, well being, and increased self-esteem that many people experience. This effect is short term, on the order 1-2 days in duration.

· Aerobic exercise increases blood supply to the brain, thus increasing oxygen and nutrient supply to the neurons, and removing metabolic waste materials from the brain.

· Aerobic exercise increases the production of neurotrophic factors in the hippocampus.

What are neurotrophic factors?

When the nerve cells are getting organized to form the organ that we call ‘brain’ (a process that doesn’t end at birth, it actually continues until about age 20), they do it under the direction and control of peptides and proteins that are secreted by the nerve cells themselves. But the job of these factors doesn’t end there: they continue to shape, modify, and re-shape several areas of the brain. They are essential for the formation of new neurons from stem cells—a process called neurogenesis. They also are important in the formation of new connections between existing neurons—a process called neuroplasticity. These two processes are important because they are the basis for learning and memory; everything we know and remember is stored in neuronal circuits. Furthermore, the thicker the connections between the neurons the faster the flow of information in the circuits—very much like the broadband required for fast transmission of electronic signals. The brain factors cause this thickening as well.

There are several known neurotrophic factors that have been shown to increase in concentration due to a sustained, long term exercise regimen:

· BDNF (Brain-Derived Neurotrophic Factor).

· NPY (Neurpeptide Y).

· VEGF (Vascular Endothelial Growth Factor).

The fact that we can identify specific brain peptides that increase neurogenesis and neuroplasticity is interesting enough. But what makes it even more fascinating is where in the brain this increase happens.

Enter the Sea Horse.

In the temporal lobe of the brain there is an area, called the hippocampus, because it is shaped like a sea horse. This area regulates emotions and stores memories. In fact, it has been known that in aging brains and in depression, two situations in which neurogenesis and neuroplasticity are reduced, the hippocampus gets smaller. Furthermore, electroshock therapy and antidepressants caused an increase in the size of the hippocampus, apparently due to increase in neurogenesis and neuroplasticity.

It was especially gratifying to read in the latest Proceedings of the National Academy of Sciences (PNAS, vol. 104, p. 4647, 2007) the report by Warner-Schmidt and Duman. The unequivocally demonstrated that the antidepressant drug fluoxetine (Prozac) and the pain-control drug desipramine (Norpramine, Pertofran), cause a large increase in VEGF in a specific area of the hippocampus (The subgranular zone). Interestingly, desipramine’s action is inhibition of pain signals ascending through the spinal cord to the brain; in other words, it inhibits the perception of pain.

Not surprisingly, aerobic exercise does the same thing. We even know how this happens on the molecular level—through the action of the very same brain factors: BDNF, NPY, and VEGF.

The take home lessons

· We now know beyond the shadow of a doubt that aerobic exercise increases the feeling of well being, increases learning capacity and improves memory.

· Aerobic exercise ameliorates depression and is becoming an additional tool in the treatment of this disease.

· Aerobic exercise reverses the effects of aging on the brain.

· Aerobic exercise may reduce the perception of pain—an important implication for people suffering from chronic pain, such as arthritis.

One final note: to all you Yoga practitioners, iron pumpers, and assorted other exercise enthusiasts—these effects on the brain were demonstrated only with aerobic exercise. Sorry.

Dov Michaeli, MD, Ph.D

More on the benefits of resveratrol - the substance in red wine that is associated with longevity. It turns out it also enhances exercise endurance -- in mice at least -- from Dov Michaeli, MD, PhD: In a paper published in the November 16, 2006 issue of the journal Cell , a team of French investigators added more fuel to the red-hot topic of resveratrol, the chemical in red wine that has been reported to have beneficial effects on longevity. The researchers, led by Dr. Johan Auwerx from the Institute of Genetics and Molecular and Cellular Biology in Illkirch, France , fed two groups of mice a high calorie diet that caused them to develop a disease similar to type 2 diabetes. One group of mice also received resveratrol in their diet; the other did not. The two groups of mice were then tested for physical endurance by running on a treadmill. The resveratrol group, it turned out, had double the endurance of the control group. Pretty impressive.

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