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I.R.F. / Aging news / General / 06010601

The Three Bridges to Longevity. Bridge One
Posted on: January 6, 2006

One way to look at our path to longevity is to regard it as a journey over three sequential bridges. Bridge One is based on therapies that exist today. Bridge One therapies consist of the best of present-day medicine, including biotechnology breakthroughs that are occurring every day. Bridge One will take us to Bridge Two, which consists of the full blossoming of the biotechnology revolution. Then Bridge Two will take us to Bridge Three, the nanotechnology/artificial intelligence revolution, which will lead to life spans that are currently incomprehensible, but which will soon be commonplace, measuring in the hundreds of years. There are several Bridge One technologies that people can do themselves without the aid of medical professionals. These include things like proper diet, caloric restriction, adequate exercise, stress management, aggressive nutritional supplementation, detoxification and proper care of your brain. There are also things that can be done with the help of medical professionals. For example, you can have your genomics tested; you can have tests done to determine specifics of your metabolism such as methylation, inflammation and glycation defects. You can undergo testing to detect heart disease early and then take measures before it has a chance to strike. You can detect and prevent cancer before it has a chance to spread. You can avail yourself of bio identical hormone replacement therapies.

Bridge One – What People Can Do Themselves

There are 4 sources of calories: carbohydrates, proteins, fats and alcohol. People can make good and bad choices for each of these types of calories. Carbohydrates, for example, are not inherently bad; rather there are good and bad carbohydrates. Similarly, proteins, fats and alcohol are not inherently bad, but there are good and bad choices within each of these categories. Whole grains like brown rice, legumes such as lentils and beans, and above-ground green vegetables are examples of good carbohydrates. They have a low glycemic index, meaning they do not turn into sugar quickly in the body. There are "bad" carbohydrates, however. Bad carbohydrates are ones which tend to turn into sugar quickly, causing excessive weight. Refined sugar, refined flour products, breads, root vegetables that grow underground, such as potatoes and beets, have a high glycemic index and are not optimal sources of energy. Consumption of these should be limited. Proteins are available in good and bad varieties. Fish and seafood, vegetable-based protein sources such as tofu and other soy products are good proteins. Less beneficial proteins are fatty red meats, which are high in saturated fat, and egg yoke, high in inflammatory arachidonic acid. There are good and bad fats. Fish and fish oils are good as are avocado and olive oils; raw, unsalted nuts and seeds contain beneficial fats. Bad fats include deep fried foods, processed vegetable oils like corn oil, and "trans" fats such as are found in margarine. People are often surprised to learn that alcohol is also available in good and bad varieties. Red wine has benefit, as it is rich in phytonutrients such as resveratrol, an anticancer agent. Beer is an example of a somewhat bad alcohol, since beer is rich in amylose, which has a high glycemic index. Although this is the conventional wisdom, this is controversial.

Caloric restriction
Caloric restriction has been proven to extend lifespan of laboratory animals. Lifespan is how long the longest living individual in a species can live. Currently, the maximum human lifespan seems to be about 120 years. No human being has ever been scientifically documented as living more than 124 years. But, like Olympic records, we expect this soon to be broken and rebroken again and again as Bridge Two and Three therapies come into their own. For now, however, caloric restriction is the only thing proven to help lifespan. For example, fruit flies have a lifespan measured in days or weeks; laboratory rodents have a lifespan of two or three years. In animal experiments involving caloric restriction, researchers were able to extend the healthy lifespan of laboratory animals and insects drastically. Increases in lifespan of 50-100 percent or more were seen. We know that consuming excess calories reduce life expectancy; conversely, restricting calories can extend lifespan, at least in laboratory animals. In yeast experiments done by David Sinclair, caloric restriction was shown to activate the SIRT1gene that expresses SirT1 deacetylase that stabilizes DNA, extending lifespan. The authors postulate that caloric restriction "could extend life-span by inducing SIRT1 expression and promoting the long-term survival of irreplaceable cells". Polyphenols are a dietary substance that also activates this gene and may extend lifespan by 70 percent in yeast. A potent polyphenol known as resveratrol is found in red wine. Rodent experiments have been done by Richard Weindrich at the University of Wisconsin, and he has done gene profiling to find out which genes are turned on and which genes are turned off during the aging process. It seems only a handful of genes are involved. By caloric restriction, he was able to show 30-50% increase in lifespan in rodents, fish, spiders and other animals. We know that in youth certain genes are active and certain genes are not, and in aging, these often change. We know that caloric restriction can move those genetic switches in older animals to more closely resemble the gene expression of a younger animal. For humans we have the results of real life experiments, not laboratory data. For example, on the Japanese island of Okinawa, a common phrase is "hara hachi bu", which means "belly 80 percent full". This concept means you should try to eat approximately 80 percent of what you would need to feel full. You try to leave the table a little hungry. The caloric intake of the average adult Okinawan is 1800 calories per day compared to Americans who eat 2500 calories or more each day. This seems clearly related to their lifestyle choices and not genetics, because as Okinawans move away from their homes on Okinawa and adopt different lifestyles, they live shorter lifespans like their neighbors. So there is nothing genetic about their long lifespans. They live longer because of their lifestyle choices, particularly caloric restriction.

Other lifestyle choices
Japan is a land of other healthy lifestyle choices – at least as far as diet is concerned. Even though many Japanese smoke and live high stress lifestyles, the number of Japanese over 100 years of age has doubled in the past five years. This is a new phenomenon felt to be due to improved health-care coupled with their underlying healthy diet. In 1998 there were 10,000 Japanese over 100 years of age. In 2003, five years later, the number had doubled over 20,000. Women, by the way, constitute 85 percent of this centenarian population in Japan. It is interesting to compare this to the United States, a land characterized by bad lifestyle choices, certainly as regards diet. A leading cause of death in the United States is, in fact, poor lifestyle choices. Half of the deaths in the US are the result of easily modifiable lifestyle choices. The number one cause of death in the US is tobacco, which causes 18.1 percent of deaths. The second is bad diet and lack of exercise, which causes 16.6 percent of deaths. Another healthy lifestyle choice that people can make is regular aerobic exercise. Proper aerobic exercise consists of getting your heart rate up to 60-80 percent of your maximum predicted heart rate (which is equal to 220 less your age) and keeping it there for a sustained period of time. Some type of aerobic exercise should be done continuously for 30 minutes at least every other day. In addition to aerobic exercise, weight training and stretching are valuable. In addition we can take nutritional supplements. Modern farming methods unfortunately have led to significant decreases in the vitamin and mineral content of our food. Also, almost no one eats enough fruits and vegetables to get adequate nutrition without taking supplementation. Chemical reactions in the body occur because of enzymes and many enzymes in the body need vitamins and minerals as cofactors in order to function properly. By taking nutritional supplements, you can ensure that the raw minerals are always available to ensure that your youth-sustaining enzymes function optimally at all times. By taking supplements we can help neutralize the now outdated genetic time bombs programmed within our genes designed to take us out of competition for scarce calories as we age. We can help accomplish some of the same goals by caloric restriction, namely turning genes of youth on and genes of aging off at least for a while. In effect, by aggressive supplementation and other lifestyle choices we're trying to "reprogram our biochemistry".

Bridge One – What People Can Do With Physician Assistance

Genomics testing
One thing doctors can do is to help people test their genes. Genomics testing tells you what genes you have. The Human Genome Project was recently completed and all 35,000 human genes have been identified. But, the key to genomics is the realization that genes just represent tendencies in most cases. Most people do not have a "breast cancer gene" or an "Alzheimer's gene". You may have a gene that increases your risk of breast cancer or Alzheimer's disease, particularly if you make the wrong lifestyle choices. But you can often change this outcome by making proper lifestyle choices. But you won't know what specific lifestyle choices to make unless you know what specific genes you have, and this is where genomics can provide critical information. Here are some practical examples of what genomics testing can tell you. The cytochrome P 450 (CYP 450) genes code for proteins that help the body detoxify toxins in the liver. One cytochrome P 450 gene is known as C17. Women who have a mutated C17 gene can have an increased risk of breast cancer or osteoporosis. If a woman performs genomics testing and finds she has mutated C17, she should avoid taking estrogen, since she would be at higher risk of developing breast cancer by doing so. Another CYP 450 gene is 1A1. Some mutations of this gene may render people much more susceptible to lung cancer. Individuals who have mutated CYP 1A1 should be especially careful not to smoke because they are at much higher risk of developing lung cancer. A mutated CYP 450 2E1 gene increases susceptibility to alcohol-related liver disease and cirrhosis. People with this mutation should be very careful with regard to alcohol consumption. So these are examples of how genomics testing can help you make specific lifestyle choices.

Early detection of cardiovascular disease and cancer
Cardiovascular disease is the leading cause of death in many developed countries. Medical professionals can help their patients avoid heart disease with early detection. The usual blood tests that are used to determine risk of heart disease (cholesterol subfractions, triglycerides, etc.) are not adequate. Highly sensitive-CRP, homocysteine and lipoprotein (a) levels need to be checked as well. In addition, the "acceptable limits" given by many reference laboratories are also often inappropriate. As one example, the reference laboratory used in medical practice considers levels of homocysteine less than 15 as acceptable; yet risk of heart disease increases with levels greater than 7.0. Cholesterol levels under 200 are considered acceptable, but levels between 130-160 may be optimal. Specific cardiovascular-related genomics tests are available as well and can provide useful patient-specific information. Recently, non-invasive test for delineation of atherosclerosis have become available. Ultra fast CT scans can quantitate the amount of calcified plaque in the coronary arteries. Virtual angiograms and MRIs are becoming available in several metropolitan areas, obviating the need for invasive angiography. Cancer is the second leading cause of death. Medical professionals can help with early detection and prevention of cancer. They can also suggest supplements like vitamin C, selenium, curcumin, fish oil, and folic acid. A diet rich in soy products and green tea is cancer protective as well. It is important to make lifestyle choices including regular aerobic exercise and strict avoidance of smoking and exposure to passive cigarette smoke as well. These are proven methods of reducing cancer risk. Physicians can help detect cancer in the very earliest stages even before a detectable lesion is present by utilizing the DR-70 test which is undergoing FDA testing as a possible screening test for colorectal cancer. This blood test only requires a few cancer cells to be present in the body for detection. This can help detect cancer in a very early stage before it has had a chance to metastasize.

Hormone replacement
High hormone levels are a hallmark of youth, while declining hormone levels are characteristic of advancing age. At around 30 years of age an individual's hormones begin to decrease, which then begins to accelerate the aging process. By restoring hormone levels to more youthful levels, people can often experience the benefits of higher hormone levels similar to what they had when they were younger. Antiaging hormones include estrogen, progesterone, testosterone, thyroid, melatonin and human growth hormone (hGH). The cornerstone of hormone replacement therapy, however, is to only replace hormones whose levels are low and for which there is a demonstrable deficiency. The indiscriminate prescribing of anabolic steroid hormones, such as human growth hormone for bodybuilders who merely wish to enhance the appearance of their physique, yet have adequate levels of hGH, is an inappropriate use of hormone replacement therapy and is not recommended. Optimally one should use bio identical hormones, hormones which are chemically identical in their structure to those found naturally in the human body. For example when prescribing estrogen replacement for women, we want to use estriol, estrone and estradiol, which are the same estrogens found naturally in the body. Similarly, we prefer to use bio identical progesterone, not a progestin like medroxprogesterone (which is not progesterone at all, but a synthetic drug, which possesses progesterone-like activity). We use testosterone itself (not medroxytestosterone), which can improve muscle mass and sex drive in both men and women. Melatonin is useful in promoting deep sleep and also fights some cancers and, in certain cases of documented growth hormone deficiency, we have found the use of human growth injections of value.

Source: T. Grossman; Latest advances in antiaging medicine; Keio J Med. 2005 Jun;54(2):85-94.
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