Monaco Anti-Aging Conference
Report from the 2nd Annual Monte Carlo Conference
By
Karen Kaufman, MS, CCN, and Ward Dean, MD
On June 23rd and 24th, 2001, several hundred physicians and scientists interested in the science of preventing aging and the diseases of aging gathered in the majestic city of Monte Carlo on the Mediterranean Sea to attend the Second Annual International Conference of Anti-Aging Medicine. The conference, which was co-sponsored by Vitamin Research Products (VRP) and Great Britains International Anti-aging Systems (IAS), brought together a number of the foremost physicians and scientists in the field of anti-aging/life extension medicine.
Ward Dean, MD, presented an overview and update of his work on the Neuroendocrine Theory of Aging, based on the concepts first elaborated by the brilliant Russian scientist, Professor Vladimir Dilman. These concepts, which should be familiar to readers of Vitamin Research News, propose that the aging process and diseases of aging are due to a loss of hypothalamic and peripheral receptor sensitivity to negative feedback over time, resulting in a shifting of homeostasis and loss of metabolic control. This results in the development of the metabolic pattern of aging, characterized, in part, by the development of insulin resistance, hyperglycemia, and hyperinsulinemia, and an overactive and prolonged stress response causing chronically elevated levels of cortisol. These are three of the Pillars of Aging, the theme of the conference. Dilmans concepts were further supported by recent research discussed by a number of conference presenters.
One consequence of hyperinsulinemia and hyperglycemia is the formation of advanced glycosylation end products (AGEs)--due to reactions of glucose and oxygen with proteins in the body. These AGEs cause inter- and intra-molecular crosslinking, believed to be a major cause of several diseases of aging, including cataracts, diabetes and atherosclerosis. This is also the basis of the Crosslinking Theory of Aging (Ward Dean, MD, Emmanuel Opara, PhD, Oxygen Free Radicals and Aging, Vitamin Research News, Vol. 12, No. 1).
The good news is that substances are now available which can not only restore hypothalamic sensitivity, resulting in normalization of many of these adverse hormonal shifts, but which can also block the formation of AGEs and reverse some of the crosslinks that have already formed. Some of these substances include guanidine, the active ingredient in Goats Rue, its close relative aminoguanidine, and the anti-diabetic drug, Metformin, which is chemically similar to guanidine. Other crosslinkage inhibitors include EDTA, known for its benefits in cardiovascular disease and as a chelator of calcium and other heavy metals, and the hydrazine derivative carnosine, which has been demonstrated to be a powerful crosslinkage inhibitor and even a breaker of pathological crosslinks. Other receptor sensitizers that were discussed are shown in Table 1 above. Regular readers of this newsletter are already familiar with most of these nutrients.
In another talk later in the conference, Dr. Dean spoke about the causes of age-related cognitive impairment and approaches to reversing these decrements. This was essentially an update of the work presented a decade ago in his landmark books, Smart Drugs & Nutrients, and Smart Drugs II, the Next Generation. The loss of cognitive function with age, now known as age-related mental decline (ARMD) is probably the single biggest concern to the aging population. Dr. Dean spoke about the latest research showing the great promise of cognitive enhancing nutrients such as DMAE, huperzine, phosphatidylserine and Acetyl-l-carnitine, as well as drugs like piracetam, Hydergine, and Lucidril.
Female Hormone Replacement Therapy: A More Natural Approach
John Lee, MD
In 1978, John Lee, MD, learned about the dangers of synthetic progestins and the potential benefits of natural progesterone from Ray Peat, Ph.D. Dr. Lee has dedicated his career to educating women and physicians about the dangers of prescribing estrogen to those who are not estrogen deficient, or in prescribing estrogen in excessive doses. Dr. Lee has also warned against using synthetic progestins (such as medroxyprogesterone acetate) instead of real progesterone.
Twenty-five years ago he (along with Dr. Peat) was a lone voice in the medical community. He was written off as a radical by his orthodox colleagues. However, recent medical evidence has vindicated him, pointing out the dangers of synthetic estrogen and progestin replacement therapy. His latest findings reinforce the importance of natural progesterone replacement for both women and men. He also explained the medical fraud being perpetrated on physicians and the public by the false claims of osteoporosis reversal by pharmaceutical manufacturers.
Dr. Lee also addressed a common mistake made when checking levels of various hormones in the serum. Pointing out that hormones in plasma or serum are bound to protein, Dr. Lee emphasizes that the physician needs to measure how much hormone is available to bind with the respective receptor sites. One accurate and economical way to know this is to check the hormone levels in the saliva. In his next book, which he co-authored with David Zava, PhD, this issue will be discussed in detail.
The Free Radical Theory of Aging
Denham Harman, MD, PhD
Attendees at the conference also had the privilege of hearing from one of most respected names in the field of biomedical gerontology, Denham Harman, MD, PhD. Dr. Harman developed the Free Radical Theory of Aging, first presented in his landmark paper in 1954, and which has been subsequently supported by a plethora of research performed by him and other scientists inspired by his work. His theory is an outgrowth of research conducted under the auspices of the Shell Development Company, a subsidiary of Shell Oil, prior to his attending medical school.
At this conference Dr. Harman was presented with an award by Princess Angela of Germany, recognizing his groundbreaking studies in the field of anti-aging medicine. His contribution to the field is immeasurable, forming the foundation upon which much of the research on which the anti-aging, health-promoting benefits of antioxidant nutrients is based. At age 85, Dr. Harman is a walking testimonial of the health benefits of these nutrients.
Macromolecular Crosslinking and Aging
Don Kleinsek, PhD
Don Kleinsek, PhD, is CEO and senior scientist of GeriGene Medical Corporation of Madison, Wisconsin. GeriGene is a leader in the field of anti-aging applications of genetic research. Prior to his involvement in genetic research, Dr. Kleinsek was an associate of the late Dr. Johan Bjorksten, the leading proponent of the Crosslinkage Theory of Aging.
In the first part of his talk, dedicated to the memory of Dr. Bjorksten, Dr. Kleinsek discussed macromolecular crosslinking and aging. He emphasized the importance of aminoguanidine, which shows great promise in being able to prevent crosslinking. He also discussed the antiaging potential of carnosine, which may not only be able to prevent this crosslinking, but in certain situations, can actually break the crosslinks that have already formed. There is very promising evidence concerning carnosine eye drops being able to dissolve cataracts without surgery. Carnosine eye drops are only available for research purposes at this time, but it shouldnt be long before these eye drops are in general distribution.
In the second part of his talk, Dr. Kleinsek presented dramatic photos of the wound-healing, wrinkle-relieving effects of therapies based on his genetic research. Moving beyond theoretical concepts, GeriGene is now in clinical studies, pending FDA approval of their unique therapeutic modalities. The skin-rejuvenating preparations from GeriGene portend a new and unique approach to anti-aging therapy, which should see wide acceptance in the years to come.
Carnosine - The New Anti-Aging Dipeptide
Marios Kyriazis, MD
In addition to running a clinical anti-aging practice in the United Kingdom and serving as President of the British Longevity Society, Marios Kyriazis, MD, has dedicated the last 10 years of his career to carnosine research. Dr. Kyriazis believes that carnosine is one of the most effective anti-aging treatments, and expects that carnosine-containing skin creams and eye drops will become available soon.
His research shows that carnosine, a di-peptide, extends maximum cell division capacity, protects against DNA oxidation and is a free radical scavenger. Carnosine inhibits the formation of carbonyl groups, thereby reducing the formation of abnormal proteins. It also blocks glycosylation and reduces AGEs, as mentioned above. Dr Kyriazis research also shows carnosine to be a cell membrane stabilizer and an intracellular buffer.
In the past, carnosine has been used to treat arthritis, stomach ulcers, myopathy, skin trauma and wounds, for radioprotection, immuno-modulation, and enhancing stamina. His work shows that the ideal dosage of carnosine is between 50 to 150 mgs. In addition, he has concluded that the activity of carnosine is enhanced by other antioxidants such as vitamin E and vitamin C and other nutritional supplements.
The uses for carnosine are numerous, and include diabetic complications, liver disease, cataracts, Alzheimers disease, and cancer. The subjects in Dr. Kyriazis clinical trials report improved well-being, enhanced muscle tone, increased hair growth, and in rare cases, improvements in sense of smell, sleep patterns and sexual enjoyment. Dr. Kyriazis also decried the claims of some purveyors of supplements who say that dosages of at least 1,000 mg are required for carnosine to be clinically effective. He cited the possibility of potential adverse effects that could result from such high doses, and presented data confirming the clinical effectiveness of human dosages in the range of 50-200 mg daily.
The Biological Basis of Aging and Aging Reversal: Clinical Evidence
Walter Pierpaoli, MD
Conference attendees were also treated to a lecture by Walter Pierpaoli, MD, titled The Biological Basis of Aging and Aging Reversal: Clinical Evidence. Dr. Pierpaolis name should be familiar to readers of Vitamin Research News, as he is one of the two leading researchers in the world known for his work with melatonin.
In accordance with the Neuroendocrine Theory of Aging (and in fact, Dr. Pierpaoli was a friend and colleague of Dilman), Dr. Pierpaoli suggests aging is a precise, genetically-determined and species dependent neuroendocrine program in the pineal network, namely in the neural structures of the brain and peripheral nervous system regulating the circadian, synchronized, rhythmic and oscillatory synthesis and secretion of all hormones, neuropeptides and any other endogenous molecule.
Dr. Pierpaoli believes that aging is a brain-programmed hormonal event, and that the program can be modified or reversed by proper reprogramming. His experiments show that melatonin can postpone hormonal aging in perimenopausal women by actually restoring the cycles in both perimenopausal and postmenopausal women. (Please do not confuse this finding with an ability to restore fertility. It is clear from his studies that he has yet to accomplish that).
Through animal experiments, Pierpaoli has become convinced that it is not just the pineal melatonin that has anti-aging properties, but other peptides released by the pineal gland as well. One such tripeptide is Thyrotropin Releasing Hormone (TRH), a molecule concentrated in the pineal gland and the hypothalamus.
Dr. Pierpaoli is convinced that supplementing with melatonin before bed can give the pineal gland a rest and help reset the hormonal clock. This will allow permanent reconstitution of immunological surveillance and maintenance of body health and integrity. In Dr. Pierpaolis opinion, The basis of health is thus the maintenance of youthful hormonal cyclicity.
S-Adenosylmethionine (SAMe) Methylation and Longevity
Richard Brown, MD
Richard Brown, MD, the author of Stop Depression Now spoke eloquently about the role of SAMe. SAMe plays a critical role in methylation (Fig. 1). Methylation is crucial for the synthesis of neurotransmitters in the brain and for the formulation of myelin and phospholipids that protect neuronal cells and aid in nerve conduction. SAMe participates with folic acid, B12 and B6 to protect the aging brain.
Studies have shown that SAMe has a profound effect on learning and memory in both young and old rats, and these findings are relevant to human aging. Dr. Brown presented data that show that oral supplementation with SAMe is well absorbed in the cerebrospinal fluid.
His own clinical experience has demonstrated that SAMe has positive effects in the elderly population with organic brain syndromes, depression, diseases of the liver, and arthritis (which is a disease of aging). Dr. Browns extensive work with SAMe has led him to conclude that it plays an important role in delaying aging.
Effect of Pineal Peptide Preparation on Life Span and Carcinogenesis
Vladimir Anisimov, MD
Professor Vladimir Anisimov, MD, DSc, has dedicated much of his career to researching the effects of pineal peptides on aging and carcinogenesis (Fig. 2). He also worked directly with Professor Dilman for seven years. The research that he and his group have been conducting for the last 30 years has further confirmed Dilmans neuroendocrine hypothesis, which continues to be revised chapter-by-chapter in this newsletter by Dr. Dean, also a co-author of Dilman.
Professor Anisimov and his group have developed a melatonin-free pineal preparation called epithalamin which acts as a hypothalamic resensitizer and has been demonstrated to extend the maximum lifespan of experimental animals. Professor Anisimov, working together with Dr. V. Khavinson, has synthesized the active ingredient in Epithalamin, which has been named Epitalon. Epitalon is a combination of the amino acids alanine, glutamine, glycine, and aspartic acid.
According to Anisimovs presentation, Epitalon has antigonadotropic effects (reduces the gonadotropins--FSH and LH--which increase with age in both men and women). Epitalon also decreases the threshold of the hypothalamus to feedback inhibition by estrogens and glucocorticoids (i.e., restores hypothalamic sensitivity), restores ovulation and fertility in old rats, prolongs reproductive function in females, increases sleeping time, increases melatonin synthesis and secretion, increases tolerance to glucose, and decreases serum cholesterol and triglycerides.
The developers of Epitalon are applying for drug approval in both Russia and the United States, but it may also become available as a nasal moisturizer or sublingual dietary supplement.
The Role of Growth Hormone in Aging and its Therapeutic Potential in the Elderly
Richard Walker, PhD
The always-of-interest update on growth hormone was presented by Richard Walker, PhD., a consultant in Medical Physiology (Endocrinology) and former director and general manager at the Clinical Alliance for Research & Education Service, Office of Research, University of South Florida, Tampa, FL.
Dr. Walkers presentation was based largely upon information learned from studies on disease-related growth hormone deficiency. Walker sees this research being tapped to help formulate a rational approach to treating age-related growth hormone deficiency. Somatotrophin is the proper name for growth hormone (GH), a natural product of the endocrine system that was originally named because of its ability to stimulate growth in laboratory animals and later, in children. Later research has shown GH to be an important hormone for proper maintenance and integrity of all systems in the body.
In disease-related growth hormone deficiency, the somatotrophic neuroendocrine axis completely stops functioning. Consequently, system-wide changes occur such as loss of muscle tone and strength, increase in abdominal fat, loss of bone, development of heart and circulatory disorders, reduced metabolism, loss of insulin sensitivity, and a reduced quality of life. When GH is given to individuals with disease-related GH deficiency (the only FDA-approved use of the pharmaceutical drug) many of the system-wide maladaptations mentioned above are reversed.
During normal aging, the homeostat that produces GH (i.e., the energy homeostat) (Walkers terminology rephrased into that of Dilman) begins to decline. This decline can be measured as early as mid-to-late 30s. That is one of the reasons why most of the system-wide changes that occur in disease-related GH deficiency can be seen in the aging population. Administration of GH in normally aging individuals should have many similar positive effects in reversing these maladaptive changes. Despite these apparent potential benefits, the FDA has not approved GH replacement for the aging population.
Dr. Walker believes that rational use of GH can be scientifically and medically justified, and is a logical course of action. If one decides to take that action, he strongly urges physician monitoring and collection of data so we can all learn the risks and benefits of such a program. Dr. Walker also presented data showing that it may be possible to reactivate the somatotrophic neuroendocrine axis in a normal aging adult through the use of Growth Hormone Releasing Factors (GHRF).
At least one pharmaceutical company is already manufacturing GHRF and participating in clinical trials. Dr. Walker also mentioned that certain nutritional supplements that contain amino acids, with particular mention of a proprietary formula of amino acids and polypeptide growth hormone precursors (ProHGH) may be a viable and safe alternative. Although pharmaceutical GH and GHRF are cheaper than they used to be, they are still prohibitively expensive.
Stopping the Number One Killer--Chronic Inflammation and Autoimmunity
Marc R. Rossellini, PhD
One of the most interesting, thought-provoking, and controversial speakers at the conference was Marc R. Rossellini, PhD, from Il Vitaforza Instituto in Milan, Italy. Dr. Rossellini suffers from a very rare form of Parkinsons Disease--Parkinsons SDS. In order to understand and treat his own illness he studied to be a neuroscientist--after reading Smart Drugs & Nutrients. He thinks outside the box established by the orthodox, conventional medical community. Rossellini believes we may have to rethink some longstanding paradigms in medicine. The complete content of his presentation cant be appreciated in this short review because of its complexity and the time constraints of the conference which prevented presentation of specific data. His concepts were provocative, however.
The topic of Dr. Rossellinis lecture was Stopping the Number One Killer--Chronic Inflammation and Autoimmunity. His hypothesis is that there is an overlooked gland in the body. That gland is the neuroendocrine immune-gastrointestinal (NEIG) axis. In addition, Rossellini speaks of the mitochondrial-oxidative-metabolic (MOM) axis. Rossellini claims it is dysregulation within these systems that results in chronic inflammation, neurodegenerative disease, and autoimmune disease. Because, he says, the gastrointestinal tract functions as the master endocrine gland controlling the entire human immune system, it is probably the first place we should look to accomplish a remission in these diseases (Fig. 3, above). Conventional medicine throws Nonsteroidal Antinflammatory Drugs (NSAIDs) at these diseases. Rossellini thinks this is all wrong. He reports that these drugs lead to a total degeneration of the GI tract, leading many physicians to prescribe H2 blockers like Zantac and Tagamet, or even stronger acid reducers called proton pump inhibitors, like Prilosec and Prevacid. Rossellini says these drugs may actually make matters even worse.
If there is no stomach acidity, there is no ability to extract the nutrients from food or supplements. Therefore, Rossellini recommends that people who suffer from these ailments should be taking a digestive aid with hydrochloric acid and pepsin. Rossellini believes the MOM axis is using up nutrients--particularly proteins and amino acids--at a furious pace. Part of his protocol often includes large amounts of the amino acid glutamine (the most abundant amino acid in the body) along with alanine. He also recommends rehabbing the gut with a good probiotic. He has found that most people with degenerative diseases have a lack of lactobacillus in their gut. He routinely recommends Lactobacillus GG (Culturelle). His protocol includes prescription hormones (especially T3) and other somewhat controversial prescription drugs (including low-dose amphetamine).
Conclusion:
A special characteristic of this meeting was that, due to the limited audience and relaxed surroundings, attendees and speakers were able to enjoy personal interactions to a greater extent than is possible at most conferences. Audiotapes of the conference will be available soon, and the Proceedings of the Second Monaco Anti-Aging Conference will be published in the near future. Although this conference is among the priciest of scientific conferences, attendees reported that it was well worth the price. Some of those who attended last years conference were heard to remark that the First Monaco Anti-Aging Conference was the best theyd ever attended, and the second conference was even better.