Every December, thousands of physicians attend what is by far the largest anti-aging conference in the world: the A4M (American Academy of Anti-Aging Medicine) conference in Las Vegas, Nevada. I have attended many of these conferences, most recently in 2012 and 2013. I will report mainly on the 2013 conference, but will include a few relevant presentations made at the 2012 A4M conference.

Nathan Bryan, PhD, (Assistant Professor of Molecular Medicine, School of Medicine, University of Texas Health Science Center) is a nitric oxide expert. Nitric oxide is a short-lived signaling molecule composed of nitrogen and oxygen. Dr. Bryan pointed to three theories of aging, all of which he said are controlled by nitric oxide: telomere shortening, mitochondrial dysfunction, and loss of stem cell function.

Telomeres are the ends of chromosomes that shorten with age, causing cells to become inactive when the telomeres become too short. Nitric oxide synthases, a group of enzymes that catalyze the formation of nitric oxide, stimulate the activity of the enzyme that keeps telomeres from shortening in endothelial cells (cells lining blood vessels).1,2

Mitochondria are organelles in cells that produce energy. Nitric oxide stimulates the creation of new mitochondria, notably in heart muscle.3

Stem cells can prevent tissue aging by regenerating damaged and worn-out tissues. Dr. Bryan said that nitric oxide synthase is required to stimulate mobilization and differentiation of stem cells,4 and that older patients dont respond well to stem cell therapy due to reduced availability of nitric oxide.

In addition to these aging processes, reduced nitric oxide availability leads to insulin resistance.5 And with age, the endothelial cells lining blood vessels show a reduced capacity to produce the nitric oxide that causes blood vessels to dilateone of the symptoms of endothelial dysfunction.6

Endothelial dysfunction contributes to high blood pressure and atherosclerosis and precedes atherosclerosis years before the disease manifests.7 Endothelial dysfunction tends to occur in men at an earlier age than it occurs in women.8

Pomegranate protects cardiovascular health by augmenting nitric oxide, which supports the functioning of endothelial cells that line the arterial walls. Nitric oxide signals vascular smooth muscle to relax, thereby increasing blood flow through arteries and veins.

Scientists have known for some time that oxidized LDL (low-density lipoprotein) can reduce the expression of nitric oxide synthase, the enzyme that produces nitric oxide from an amino acid called arginine. Recently, they discovered that pomegranate juice enhances the bioactivity of nitric oxide synthase in endothelial cells. Furthermore, pomegranates antioxidant properties protect nitric oxide from oxidative destruction, thus augmenting its biological actions.9,10

An Italian study examined the role of pomegranate juice in nitric oxide synthase activity in artery sections that had already developed atherosclerosis. In these segments, blood forcing its way around atherosclerotic plaque buildup exerts significant stress on arterial walls. This stress reduces nitric oxide synthase expression and sets the stage for the formation of yet more plaque.

The researchers selected mice with a genetic predisposition to developing atherosclerosis. They put the mice in one of the groups on a high-fat diet, let arterial disease develop for six months, and then added pomegranate juice to the experimental groups drinking water for 24 weeks. The placebo group was given plain drinking water.11

Pomegranate not only increased the expression of nitric oxide synthase in both healthy and atherosclerotic blood vessels, but increased it the most in blood vessels with the most plaque buildup. The list below shows the increase in nitric oxide synthase expression that occurred in response to pomegranate:8

Pomegranates ability to increase nitric oxide synthase resulted in a significant reduction in atherosclerotic lesions.11

Mark C. Houston, MD, (Associate Clinical Professor of Medicine, Vanderbilt University School of Medicine, and Director of the Hypertension Institute, Saint Thomas Hospital and Health Services) said that high blood pressure is due to three stressors to the endothelial cells that line blood vessels: inflammation, oxidative stress, and immune dysfunction.

Dr. Houston said that endothelial dysfunction precedes high blood pressure by decades.12 Once high blood pressure develops, blood vessel disease gets worse, creating a vicious cycle.13 To the extent that inflammation is part of this vicious cycle, high blood pressure is an inflammatory disease.14

Dr. Houston described different methods of measuring blood pressure. Manual measurement of blood pressure in a medical office is the worst method. The white-coat response (anxiety in reaction to medical professionals) can result in an elevated blood pressure reading leading to unnecessary drug therapy.15 This effect can be eliminated by the use of an automated device.16 Even better is a blood pressure monitoring device that can be worn over a 24-hour period.17 Patients whose blood pressure does not decrease while sleeping are more likely to have a stroke.18 Unfortunately, wearing a blood pressure monitoring device at night can often disturb sleep, undermining the accuracy of the reading.19

Dr. Houston has had great success in getting his patients off blood pressure drugs with his program of diet, exercise, weight reduction, and supplements. After six months of his treatment protocol, 62% of his high blood pressure patients were able to stop taking drugs.20 According to Dr. Houston, the average American is consuming about 10 times the minimum requirement for sodium, and is consuming two times as much sodium as potassium. Consuming five times more potassium than sodium is recommended. For blood pressure reduction, Dr. Houston also recommends omega-3 fatty acids (especially DHA), a monounsaturated fat (such as olive oil), vitamin C, vitamin D, lycopene, pycnogenol, coenzyme Q10, and 500 to 1,000 mg per day of magnesium.20

Abraham Morgentaler, MD, (Associate Clinical Professor of Urology, Harvard Medical School) has helped revolutionize testosterone replacement for older men. Prior to the 1990s, it was commonly believed that administering testosterone increased the risk of prostate cancer. Dr. Morgentaler began questioning this belief when he found evidence of prostate cancer in biopsies in men having low testosterone. In 1996, he published a paper in the Journal of the American Medical Association, which documented prostate cancer in 11 (14%) of 77 men with low testosterone.21 This result suggested to him that low testosterone is a risk factor rather than a protective factor for prostate cancer.

A decade later he was able to report that clinical trials with testosterone replacement therapy showed no increase in risk of prostate cancer.22High serum testosterone is not associated with a risk of developing prostate cancer.23,24 Testosterone replacement therapy does not even increase cancer in men with a high risk of prostate cancer.25,26

Dr. Morgentaler hypothesized that testosterone can facilitate prostate cancer if given to men with extremely low levels of testosterone. But this effect quickly reaches saturation due to the limited number of testosterone receptors. His analogy is that once a plant is receiving enough water, additional water does not make the plant grow more.27

Whereas normal blood testosterone is typically well above 450 ng/dL, saturation is estimated to occur at 230 ng/dL total serum testosterone.28 For this reason, a man with serum testosterone of 250 or 300 ng/dL would be testosterone deficient, but would be above the level at which testosterone therapy could increase prostate cancer risk. An estimated 20% of men have low testosterone by age 50, while half of men have low testosterone by age 80.29 Low testosterone levels are associated with decreased muscle mass, low bone density, central obesity, insulin resistance, low energy, decreased cardiovascular health, low libido, and irritability. Also, it is associated with increased mortality in the elderly population.29,30

In 2004, Dr. Morgentaler was writing a review of evidence for the safety of testosterone replacement therapy31 when it occurred to him to search for the basis of earlier beliefs that testosterone therapy would increase prostate cancer risk. He discovered the source to be a single study based on a single unrepresentative patient in 1941 by Nobel Laureate Charles Brenton Huggins.32

Dr. Morgentaler gave presentations at both the 2012 and 2013 A4M. About 85% of his 2013 presentation was identical to his 2012 presentation. Most of the new material in his 2013 presentation was a response to a recent article claiming that testosterone therapy increases cardiovascular disease risk.33 Dr. Morgentaler cited evidence to the contrary,29,34 calling the study flawed. His opinion was shared by other scientists.35,36

Joseph Maroon, MD, (Professor of Neurological Surgery, University of Pennsylvania School of Medicine) addressed the question, Should you allow your child to play football? Dr. Maroon cited the risks, but also extoled the benefits, which are not as easily scientifically documented.

Between 1980 and 2006, out of millions of players, there were 1,866 documented deaths or survived cardiac arrests in American competitive athletics; 56% of these deaths were due to cardiovascular disease, compared to 22% caused by trauma.37 Cardiovascular deaths in athletes under age 40 are usually due to inherited conditions.38 Retired professional football players, however, suffer more cardiovascular disease than the general population their same age.39 The injury rate among American high school athletes in the 2005-2006 school year was highest in football (4.36 per 1,000 athletes), followed by wrestling (2.5 per 1,000 for boys).40 Dr. Maroon stated that injuries from riding bicycles exceeded those from football and asked, Should you allow your child to ride a bicycle?

Dr. Maroon has devoted a great deal of attention to the subject of concussion. Long-term consequences of concussion include brain pathology from tau protein that is similar to what is seen in Alzheimers disease.41,42 Dr. Maroon recommended omega-3 fatty acids to reduce possible effects of concussion.43,44 He also referred to the Lystedt Law, passed in Washington State in 2009 (and subsequently passed in most other states), requiring that athletes under the age of 18 who have experienced a concussion during a practice or game be prohibited from further participation until cleared by a medical professional.45 The majority of coaches were already avoiding returning an athlete to play too soon after a suspected concussion.46

Dr. Maroons concluding remarks included a personal testimony regarding the benefits to health and character resulting from his lifelong participation in athletics. He contrasted the alarming growth of childhood obesity with the health benefits, social skills, and leadership skills that arise from athletic competition. He quoted General Douglas MacArthur, who wrote, Upon the fields of friendly strife are sown the seeds that upon other fields, on other days, will bear the fruits of victory.

Daniel Amen, MD, (Psychiatrist and Medical Director of Amen Clinics, Inc.) spoke at the 2012 Las Vegas A4M conference with a message that conflicted with Dr. Maroons. Dr. Amen said that, You should only allow your kids to play tackle football if you dont like them. He added that brain damage can occur even without concussion, referring to disrupted white matter found in the brains of soccer players rather than swimmers.

Dr. Amen specializes in SPECT (Single Photon Emission Computed Tomography), which uses gamma rays to image the brain. He has established that SPECT is superior to other brain imaging techniques, namely CT (Computed Tomography) or MRI (Magnetic Resonance Imaging), for the detection of mild traumatic brain injury.47 SPECT accuracy in diagnosis of Alzheimers disease may be as high as 88%.48 Dr. Amen is critical of other psychiatrists for not examining the organ which they are studyingthe brain.49 Dr. Amen believes he has established that SPECT can reveal undetected brain traumas, brain toxicities, and other maladies leading to psychiatric symptoms.50 Dr. Amen has determined that overweight and obese persons have smaller brain volume and reduced brain blood flow.51,52 Dr. Amen has also shown reduced blood flow in the brains of retired professional football players, which he says is consistent with a pattern of chronic brain trauma.53 Dr. Amen said that helmets prevent skull fracture, but not brain injury. The skull is hard, whereas the brain is soft and when there is trauma to the head, the soft brain slams up against bony ridges. In his experience, many psychiatric problems can be traced to undetected head traumas. He reported improved blood flow in retired professional football players who he treated with fish oil, multiple vitamins, ginkgo, alpha lipoic acid, and N-acetyl-cysteine.54

Michael Murphy, PhD, (Group Leader, Medical Research Council Mitochondrial Biology Unit, Cambridge, England) said that many aging-related diseases are the result of increasingly dysfunctional mitochondria (the organelles that provide energy to cells). Because getting drugs or nutraceuticals into mitochondria can be difficult, Dr. Murphy (as a mitochondrial biochemist) designed a new antioxidant molecule tailored for entering mitochondria.55,56 He called his new molecule MitoQ.57 Modeling a variety of diseases in mice and rats, Dr. Murphy demonstrated the potential benefit of MitoQ against cardiac ischemia-reperfusion,58 sepsis,59 diabetic nephropathy,60 multiple sclerosis,61 inflammatory bowel disease,62 metabolic syndrome,63 and alcohol-induced liver damage.64 MitoQ became the first molecule designed to reduce mitochondrial oxidative damage to enter phase II clinical trials. One trial, intended to reduce Parkinsons disease, failed to show any benefit,65 probably because the neuron damage in the patients was already too great for the chemical to have an effect. But the other trial, on hepatitis C, demonstrated that MitoQ could decrease liver inflammation in patients suffering from the disease.66 Future clinical trials are planned.

John Cline, MD, (Medical Director, Cline Medical Center, Nanaimo, BC, Canada) described his methods of detoxification. Dr. Cline is more representative of alternative medicine than the other presenters. Chelation therapy (removal of toxic metals from the blood) is part of his practice. Dr. Cline also recommended infrared saunas for elimination of toxic metals from the body.67 Arsenic, cadmium, lead, and mercury are toxic metals that have no known beneficial effect in humans, but which can be removed from the body through sweating.68

The human body normally detoxifies chemicals through two-step metabolic processing in the liver, described as phase I and phase II biotransformation. First, phase I causes a chemical alteration of the toxin through oxidation, reduction, or hydrolysis. Then phase II causes conjugation (linking) of the parent molecule or the products of phase I to another molecule, such as glutathione or sulfate.69,70 Phase II results in products that are much less toxic, water soluble, and easily excreted. But the products of phase I metabolism can be more toxic than the original toxin. To protect against the toxic products of phase I, Dr. Cline recommended magnesium, zinc, folic acid, vitamin C, and B vitamins. For phase II products, he recommended whey protein, N-acetyl-cysteine, glycine, pantothenic acid, magnesium, and TMG (trimethylglycine). Dr. Cline gave no citations to justify these claims.

Dr. Cline also advocates promoting forgiveness for stress-reduction and health.71 Unforgiveness is distinguished from anger by continuing rumination about the hurtful experience and offending person.72 As general advice for detoxification, Dr. Cline suggested drinking pure water, eating organic foods, avoiding amalgam dental fillings, and being cautious when eating fish (due to mercury toxicity).

Kathleen Collins, PhD, (Professor, Department of Molecular and Cellular Biology, University of California, Berkeley) spoke at the 2012 A4M about the potential for monitoring telomere length in medicine. Telomeres are strands of DNA at the ends of chromosomes that shorten with each cell division. When telomeres become too short, cells no longer divideand this effect is considered to be a cause of aging.73

Dr. Collins achieved fame by showing that defects in telomerase (the enzyme that lengthens telomeres) are linked with a genetic disease called dyskeratosis congenita, which is associated with bone marrow failure.74 Later it was shown that short telomeres could be used as a means of identifying patients who have the genetic defect leading to bone marrow failure.75 Dr. Collins said there is evidence that telomere length could be used as a diagnostic tool to identify women who have genetic defects that make them at high risk for developing breast cancer.76,77 She noted that short telomeres can be indicative of an unhealthy lifestyle, including smoking, obesity, consumption of processed meats, and a low intake of vitamin D or omega-3 fatty acids.78 Dr. Collins believes that measuring telomere length could be a useful tool in the coming age of molecular medicine based on the genomic, metabolic, and antibody profile of individual patients.79 But she said that too often, the average telomere length is used as a diagnostic tool rather than the lengths of the shortest telomeres in cells. Determining the length of the shortest telomeres is important because it is the shortest telomeres that cause cells to become dysfunctional.80,81 At the conference, Dr. Collins was representing the company Life Length (www.lifelength.com), which specializes in measuring shortest telomeres. Dr. Collins was occupying the Life Length booth in the A4M exhibit hall.

Mark Rosenberg, MD, (Physician, Institute for Healthy Aging, Boca Raton, Florida) noted that although telomerase is present in the great majority of cancer cells, short telomeres can lead to cancer by causing chromosome abnormalities.82 A study of average telomere length of white blood cells showed that the group of people with the lowest third of telomere lengths were three times more likely to get cancer and two times as likely to die of cancer over a 10-year period as people in the highest third of telomere lengths.83 Similarly, persons whose white blood cell telomeres are short have a higher risk of developing coronary heart disease,84,85 and are eight times more likely to die of infectious disease.84 Mice that were bred to be cancer resistant had their life spans increased by the telomerase enzyme (which lengthened their telomeres).86

There is a concern that lengthening telomeres by increasing telomerase activity can facilitate cancer. But mice whose telomerase activity was increased by gene therapy at 1-year or 2-years of age had a 24 or 13% (respectively) increase in median life span without increased cancer risk.87 In adult mice, at least, increasing telomerase activity had health benefits without increased cancer risk, which could be a promising sign for humans. The health benefits for the mice included increased insulin sensitivity and improved neuromuscular coordination.87 Dr. Rosenberg gave evidence of increased telomere length in people who take supplements. Average white blood cell telomere length was 5% longer for women who took multivitamin supplements, and higher dietary intakes of vitamins C and E were also associated with longer telomeres.88 Longer telomeres were associated with higher plasma levels of folic acid, vitamin D, and omega-3 fatty acids, as well as higher dietary intake of magnesium and curcumin.89

William Andrews, PhD, (Founder and President of Sierra Sciences) believes that human health and longevity without risk of cancer can be achieved by activating telomerase, the enzyme that lengthens telomeres. He noted that telomerase is active in lobsters, which continue to grow throughout their whole lives, rather than ceasing to grow at an age of maturity.90 But lobsters do not get cancer, even in polluted waters that increase cancer in fish and molluscs.91 Dr. Andrews created his company Sierra Sciences for the purpose of discovering chemicals that could increase the activity of telomerase enzyme.92 Telomerase preferentially lengthens the shortest telomeres in human cells.93 The highest potency substance Dr. Andrews has found so far is a chemical that stimulates telomerase activity to 16% of the amount that would be required to make cells immortal. He believes that with $30 million he could achieve 100%.92

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