The Life Extension RevolutionJune 2005
By Matt Sizing
Stopping Disease at the Cellular Level
“To maintain our youthful vitality as we get older, we also want to take care that the bright future is not dimmed or diminished by disease,” says Dr. Miller. Thus, the second part of The Life Extension Revolution presents a multifactorial approach to disease prevention extending all the way down to the human cells, the smallest units of living matter capable of functioning independently. Separate chapters are devoted to four key molecular or biochemical processes—oxidation, inflammation, methylation, and glycation—that are central to aging and many diseases of aging.
More than 50 years ago, Dr. Denham Harman’s “free radical theory of aging” dramatically altered how people think about aging. In studying radiation sickness in laboratory mice, Dr. Harman noticed that radiation exposure produced an onslaught of unstable molecules known as free radicals. Over time, free radicals can disrupt the functioning of cells and tissues, causing severe symptoms and even death. Oxidation caused by free radicals can impair the functioning of cell membranes, DNA, enzymes, protein synthesis, and mitochondrial function. Poor diet, aging, intense exercise, exposure to toxins, and illness all increase the risk of oxidative stress. In the last half-century, countless studies have implicated cumulative free radical damage in the development of common diseases of aging such as cancer, heart disease, diabetes, and Alzheimer’s.
Preventing free radical damage is a cornerstone of any program to prevent disease and forestall the aging process. Key strategies to reduce oxidative stress include consuming chemical-free foods and liquids, and limiting exposure to ultraviolet radiation and other environmental toxins. An overlooked yet essential tool in counteracting free radical damage is to increase the body’s store of antioxidants, which quench free radicals before they can cause harm. Supplementing with potent doses of gamma tocopherol, lycopene, and green tea, with minerals such as selenium, zinc, and manganese, and with mitochondrial energizing agents such as coenzyme Q10, lipoic acid, and acetyl-L-carnitine, is essential to counteracting free radicals. Antioxidant phytochemicals such as resveratrol, grape seed, lutein, and zeaxanthin afford additional protection against free radicals. While these phytochemicals are contained in fruits and vegetables, most people cannot possibly hope to derive from dietary sources the amounts required for optimal antioxidant protection. Thus, Dr. Miller offers a compendium of antioxidants and the recommended dosages of each needed to “rust-proof” your cells and provide the best possible protection against the damaging effects of cellular oxidation.
Life Extension has long warned its members about the lethal dangers of systemic inflammation, yet this precipitator of diseases such as cancer, Alzheimer’s, heart disease, and even arthritis is only now gaining widespread attention. Controlling inflammation is central to disease prevention and life extension. The good news is, inflammation itself is a highly treatable, correctable condition.
Keeping inflammation in check requires careful and ongoing monitoring of critical blood markers such as C-reactive protein and fibrinogen. Undisputed yet often ignored research shows that even slightly elevated levels of these blood markers can double heart disease risk, even in those with no other risk factors such as high cholesterol. A comprehensive program for controlling inflammation has as its foundation regular blood testing to assess and monitor these and other important markers of inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin can play a critical role in reducing inflammation and lowering risks for inflammation-implicated cancers of the colon, prostate, breast, and esophagus by a remarkable 50-90%. With about 150,00 Americans dying each year from these four cancers alone, the cancer-preventive effects of these NSAIDs cannot be underestimated.
After examining the benefits and potentially lethal side effects associated with controversial COX-2 inhibitors and statin drugs, Dr. Miller offers supplemental and dietary strategies demonstrated to markedly reduce inflammation. Supplements such as omega-3 fatty acids, bromelain, ginger, curcumin, DHEA, vitamin K, and ginkgo biloba all have shown powerful anti-inflammatory effects. Likewise, a diet that emphasizes monounsaturated fats (such as those found in fish and olive oil) and low-glycemic foods (such as whole grains and vegetables), while limiting foods that are high in arachidonic acid (such as fatty cuts of red meat), can provide powerful protection against the insidious consequences of chronic inflammation.
Until recently, few outside the field of molecular biology were familiar with the process of methylation, which involves the transfer of a methyl group (one atom of carbon attached to three atoms of hydrogen) from one molecule to another. Today, every health-conscious adult has good reason to be familiar with it. “Your body depends on methylation to detoxify carcinogens and other poisons, to repair damaged DNA, to form new cells, and to manufacture important anti-aging hormones,” explains Dr. Miller. “Inadequate methylation is one of the primary preventable causes of premature aging and disease.” For example, when healthy methylation patterns are disrupted, homocysteine levels increase. Fortunately, we can greatly enhance methylation by arming our bodies with several nutrients that support this critically important process.
All the way back in 1981, Life Extension advised its members to take steps to lower blood levels of an amino acid called homocysteine. Overlooked research begun in the late 1960s by Harvard pathologist Kilmer McCully argued that elevated homocysteine is a more accurate, meaningful predictor of heart attack and stroke risk than is cholesterol. Homocysteine provokes chemical reactions that damage the endothelial cells lining arterial walls, thus encouraging the formation of cholesterol deposits. As Dr. Miller deftly explains:
“McCully pointed out that cholesterol begins to build up inside blood vessels only if the blood vessel walls have been damaged. Lowering cholesterol may slow the accumulation of cholesterol deposits on the walls of the damaged arteries, but it does nothing to stop the initial damage from occurring. As such, focusing heart disease prevention efforts on lowering cholesterol is like trying to prevent rain with an umbrella.”
Countless clinical studies over the last two decades have borne out McCully’s research and Life Extension’s pioneering advocacy. Today we know that elevated homocysteine not only elevates cardiovascular risk factors, but also is linked to Alzheimer’s disease, osteoporosis, Parkinson’s disease, depression, and other potentially lethal conditions. The first step in controlling homocysteine is to have your blood tested for it. While low homocysteine indicates healthy methylation, high homocysteine signals impaired methylation and elevated disease risk. Even so-called “normal” levels of homocysteine elevate risk; in fact, a person with a “normal” homocysteine level of 10 mcmol/L of blood has twice the risk of heart disease as someone with an optimal level of 6.3 mcmol/L or lower.
Aggressive supplementation with folic acid and vitamins B6 and B12 is usually enough to keep homocysteine from posing an extreme risk. To bring your levels into the optimal range, Dr. Miller recommends an “advanced pro-methylation protocol” including trimethylglycine (TMG), a methyl donor that helps to remethylate homocysteine back into methionine. After debunking common myths about cholesterol and cholesterol-lowering drugs propagated by pharmaceutical companies, Dr. Miller demonstrates how nutrients can safely and effectively optimize levels of total cholesterol, LDL (low-density lipoprotein), and other blood lipids without the potentially harmful side effects of prescription drugs.
Glycation is another overlooked biochemical process that, like methylation, is critical in determining how quickly our bodies age and their ability to stave off the diseases of aging. Specifically, glycation “is a chemical reaction in which molecules of sugar and protein get tangled up, resulting in deformed and nonfunctioning molecules.” Glycated proteins then fuse together in a process known as cross-linking. As more glycated proteins cross-link, body tissues become increasingly stiff and tough. Glycation damages organs such as the heart, eyes, and skin, which require flexibility for optimal functioning.
“Glycation is now known to be a primary factor in the development of many age-related diseases, including atherosclerosis, heart failure, Alzheimer’s disease, complications of diabetes, cataract formation, and premature aging of the skin,” explains Dr. Miller. While glycation can never be entirely prevented, the overconsumption of sugary foods that typifies the modern American diet “promotes glycation like pouring gasoline on a fire, directly contributing to the modern epidemics of obesity, heart disease, and [type II] diabetes.”
In addition to avoiding sugary foods and refined carbohydrates, we can protect against glycation by supplementing with nutrients such as carnosine. By offering itself as a target for glucose molecules that normally would cross-link to proteins in the process of glycation, carnosine may be one of the most-effective anti-aging nutrients available today. Carnosine protects proteins in the eye against glycation, shields tiny blood vessels in the brain from damage that can lead to Alzheimer’s disease, relaxes and dilates blood vessels leading to the heart (thus increasing blood flow and enhancing the heart’s ability to contract and pump blood), and prevents skin aging and wrinkling by inhibiting the cross-linking of collagen, thus preserving the skin’s elasticity. Carnosine is also a strong antioxidant, and particularly potent against the destructive hydroxyl radical. Also addressed are anti-glycation drug therapies such as aminoguanidine, which inhibits glycation and is approved for use in Europe, and alagebrium (formerly known as ALT 7111), a newer drug under development.
Dr. Miller concludes his discussion of glycation and other correctable risk factors by pointing out that “these silent cellular mechanisms can undermine the body’s function and erode your health. By taking steps now to prevent oxidation, reduce inflammation, enhance methylation, and prevent glycation, you can improve your chances of living a long and healthy life.”
Individualizing Your Anti-Aging Program
This section of The Life Extension Revolution integrates the anti-aging and disease-prevention therapies discussed earlier into “a complete program of supplements, dietary recommendations, and lifestyle habits that will help you grow old without aging.” Detailed testing protocols, supplement regimens, and lifestyle recommendations provide a foundation that will enable every reader to develop a customized anti-aging program: “your passport to a long and vibrantly healthy life.”
Medical Testing for Aging and Risk Factors
Medical testing is an integral part of a successful anti-aging program. “Testing allows us to assess your aging status and identify risk factors for disease, customize your protocols, and monitor your ongoing progress and the effectiveness of your program,” explains Dr. Miller. “To implement an anti-aging program without benefit of this information is like driving with a blindfold on.”
Detailed testing protocols are organized into three categories:
For each testing protocol, “normal” reference ranges (used by conventional medicine to signify the absence of disease) and “optimal” ranges (used by anti-aging medicine to promote and preserve health) are provided. “The goal of this program is for you to enjoy vibrant good health throughout a long lifetime,” explains Dr. Miller. “That means that most of the standard reference ranges must be discarded in favor of optimal ranges.”
Working with a qualified physician to measure, assess, and correct your medical tests is strongly recommended. This emphasis, Dr. Miller says, “is not meant to discourage or disempower you—quite the opposite”; obtaining the best results from your anti-aging program simply means working “with a doctor who understands the difference between normal and optimal and is willing to take preemptive action against aging.”
Also included is valuable information on when to have your testing done (to establish a baseline, during the implementation phase to fine tune protocols, and annually to monitor your progress). Because different testing laboratories use different reference ranges, information is provided on how to make sure that you are comparing “apples to apples” in interpreting your test results.