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Alexander N. Asanov, Ph.D.
President and Scientific Director, TIRF Labs, Inc.
106 Grendon Place, Cary, NC 27519-6945
This topic is as old as mankind. In all of times, in every nation, people who valued their life were in quest for the fountain of youth, willing to live longer in good health and with young energy. Not surprisingly, the literature on longevity is already enormous and rapidly growing. The recent progress is fantastic. I have no doubt that my children will live 150-200 years or more. I have six; three of them are still minor. I have to take them to universities and help them to start their lives. There is a joke: “Jerks are those parents, who do not support their kids till retirement.” There is a lot of truth in this joke. In modern world, it is not sufficient to give birth. You have to equip your child with a set of skills and habits to succeed in their lives to continue your line. The kids are our tickets to the eternity.
Thus, I have six reasons to live longer and maintain good health and high productivity. Several yeas ago I started to collect and analyze the literature on longevity. The literature turned to be huge. The amount of data is enormous and rapidly growing. It is not a trivial task to navigate in this ocean of data. Unfortunately, there are numerous misconceptions - underwater rocks you want to avoid. On the other hand, there are paradise islands you want to dwell in. There are other ships sailing in the longevity ocean. Certainly, longevity programs of Calico, the NIH, and other laboratories, big and small, will result in revolutionary new findings and practical methods to increase longevity to 150, 200 or more. However, a substantial body of scientific evidence has already crystallized that suggest that you can do NOW and HERE a lot of practical and relatively simple things that will allow you to add minimum 20-40 years to your life. I mean active life in good health and young energy.
We envision that iDiagnostics will be an essential tool for longevity studies and individual longevity efforts. Using iDiagnostics you will be able to design and fine tune individualized longevity program, which corresponds to unique set of properties and perculiarities of your body. However, you do not have to wait. You can start doing good things for your healthier and longer life right now. The purpose of this webpage is to share with you my finding and my own thoughts. I would appreciate your feedback, comments, your thoughts, and your findings on longevity. Please email me to firstname.lastname@example.org.
As a scientist, I am interested in understanding the broad range of material interactions at different levels, especially at the level of the molecular mechanism, since I am looking at molecular interactions in my research. However, the fantastically complex phenomenon of life cannot be reduced and explained at the level of interactions between molecules. There is substantial body of evidence, which suggests that our mind, strong faith, or terrible fears can significantly affect our physiology and even our biochemical reactions. It would be extremely exciting to study these dependencies and to utilize them for longevity studies. In this paper I will focus on molecular aspects of aging. Below, I will tell about my vision of the molecular aspects of aging. It is an extremely complex and multidimensional process, which we have only recently began to study in depth. As a scientist and a human being, I realize that life of human beings and other living creatures cannot be reduced to molecules, cells, tissues and organs. There are powerful dimensions of our minds, spirits, emotions, conscience and sub-conscience that via nervous system control our bodies. Our bodies consist of approximately 2 million unique proteins. 80% of these proteins build the nervous system. It is extremely complex and powerful. Great discoveries will be made in these areas. They will allow to increase the lifespan dramatically.
To initiate this discussion, to make it interesting to you, I would like to share with you my practical findings about the longevity drugs, substances, food additives, and lifestyle. I have analyzed the literature and other sources on the effects of different substances on longevity from the standpoint of: “Do no harm.” My mother taught me this ancient principle. She was a medical doctor, an extraordinary ophthalmologist. I was raised between home and her clinics, absorbing many good medical principles from her and her colleagues. “Do no harm” is my main criterion for ranking the longevity substances. At the first place, they should not be toxic or harmful. Below is my list. Later, I will add more details, references to the literature, figures, and video. I will summaries your comments, if I receive them from you.
Certainly, our diet and our lifestyle critically affects our longevity and health. They also depend not only on what we eat, but also on what we think. One can say that approximately 1/3 of our health and longevity depends on our genes, the other third depends of what we eat, how we sleep, exercise, on the quality of air we breath, and water we drink. I am not sure about the percentage, but am confident that one third or even more depends on what we think. Our perception of our own age, our own mental settings for the near and remote future are extremely powerful factors. They do affect our longevity and health, energy and productivity. “Our life is what we are doing of it” - this saying is true for health and longevity. We will elaborate on this topic later.
Before we elaborate on diet, I would like to mention about magnesium. Magnesium is an element , which is as important for normal body functioning as calcium. However, magnesium is frequently under-appreciated. Since chlorophyll - the main green pigment in plants contains chelated magnesium, it is good idea to consume sufficient amount of green plants.
Individualized, precision, preventive, decentralized medicine of the future. Today, we know that extremely complex and intricate pathways are the molecular basis for our uniqueness. People have suspected this for centuries. Now we know that this is true on the molecular level. Every one of us is truly unique. We respond differently to everything, including prescription and over-the-counter drugs. My wife and my children respond well to the Tylenol. But Tylenol does not help me. Ibuprofen does. This situation projects bigger picture: we all respond differently. In this country we pay near $350 Billion annually for the prescription drugs; but approximately 1/3 of them do not work. Nearly $120 Billion are wasted. Moreover, many of the drugs cause toxic side effects that poison or even kill thousands of patients per year. Precision medicine is an urgently needed change to the healthcare. It is necessary to save lives of thousands of patients who are currently dying or are poisoned with the drugs that are good for other patients, but are too toxic to them. We have acquired sufficient knowledge to understand molecular mechanism and the diversity of these mechanisms that are making everyone of us unique. In scientific laboratories and centralized clinical facilities, we are capable of measuring individual responses. However, expensive analyses in centralized labs will not solve the problem. We need a diagnostic technology, such as iDiagnostics which every family could afford, similar to the pregnancy test, but for accurate and rapid detection of a broad range of diseases and conditions, which would be also capable of detecting predictive markers.
Before such gadget becomes an indispensable part of medicine cabinets, we should rely on less precise tools, including signals that our body sends. In the near future, we will elaborate on this topic as well.
While most of the things that can be done in the area of longevity require serious scientific studies and sophisticated expensive tools, there are some areas that can be improved just by using the power of our intellect. Cholesterol and statins give an excellent example for such intellectual gymnastics. Briefly, everyone can come to right conclusion and understand that there was major error made in the area several years ago. Since then the error has propagated over the entire world. Everyone can realize that the notations “bad cholesterol” and “good cholesterol” are similar to sayings “bad water” and “good water.” Water and cholesterol are essential construction materials for every mammalian cell. Plants can live without cholesterol; humans cannot. The modern medicine implanted into our brains these absurd notations of “bad cholesterol” and “good cholesterol” so deep that many of us have got used for them and do not question this absurd anymore. Based on this error, pharmaceutical sector created an industry of statins, allegedly to combat imaginary “bad enemy” - cholesterol. The statins generate almost $2 Billion annual income. The system does not want you to be smart and question: “are the statins good for me?” If you ask, it will be more difficult to make you to pay for these useless drugs. They do not want you to read the literature. Although most of the data are in public domain, the system does not want you to obtain and analyze the data to see that all statins are useless. They do not want you to realize that two outstanding U.S. presidents have died, likely prematurely, because of the misconception of “bad cholesterol”-”good cholesterol.” The system has established $2B industry (just small part of $350B), and they do not want to change it. Your medical doctor, who is the good one, a very helpful and nice human being, receives a slice of this pie. Your medical insurance provider receives an even bigger slice. Thousands of pharma lobbyists have been hired to influence our elected lawmakers in Washington DC to vote in favor of deteriorating laws that will further support the error and the $2B industry, which has been built on it. It is not simple to stop this machine. Remember, the cholesterol is just one of examples. There are hundreds of similar die-hard errors and misconceptions. We can not change it overnight. However, gradually we will, and we should. It is time to make the economy of this country moral.
Nevertheless, even navigating between the underwater rocks of errors and misconceptions, even operating with imprecise data, we can do a lot for our own longevity, good health, happier life, more productive work, right now, right here, where you are.
Microbiome. There is substantial body of evidence, which suggests that 10-100 trillion microbes that virtually share with us our body, play important positive role in our health and longevity. The microbes are everywhere, in our mouth, stomach, intestine, in our ears and eyes, everywhere on the skin. Remember, the notations “bad cholesterol”-”good cholesterol”? The same is applied to the microbiome. Good microbes will cooperate. In fact, they are so essential to your health that without them it is too difficult to keep you healthy. Bad bacteria can kill you or make you sick. A number of recent studies demonstrated that microbes in GE system dramatically affect even intellectual and academic capabilities of young children. We will elaborate on the microbiome topic too.
Thus, there are numerous areas that are closely related to longevity. We will add more details and new thoughts as this web page matures. Meantime, there are many practical things that can be done today to begin the endless work on the extension of life, being in good health, and keeping high productivity.
Let us begin from the substances, including drugs. I ranked them in accordance with my own experience and my specific tolerance to these substances. Your responses can differ.
Longevity substance number 1- Vitamin C - ascorbic acid. Vitamin C is a highly potent antioxidant. It has been shown to protect against various forms of cancer, and to extend the lifespan in laboratory animals. Vitamin C appears to be uniquely non-toxic compound. It is difficult, if not impossible to obtain a toxic concentration in blood taking Vitamin C by mouth. Moreover, very high concentrations in blood that were obtained by intravenous (IV) infusion of Vitamin C have been shown to be non-toxic to healthy cells and tissues. However, large doses of Vitamin C selectively killed cancer cells. It appears that high IV dosages of Vitamin C might be a sensible alternative to extremely toxic anti-cancer chemotherapies.
Longevity substance number 2 - Melatonin. Melatonin is the most documented anti-aging therapy. The literature on Melatonin is vast and rapidly growing. Similar to Vitamin C, Melatonin is a highly potent antioxidant, which protects against neurological aging. There is data showing that Melatonin protects against every known age-related disease. Melatonin has been shown to extend lifespan in laboratory animals. Melatonin also regulates night sleep and other circadian rhythms. Although there has been no evidence of toxicity in any of the published studies on Melatonin, my personal experience showed discomfort of large doses. If I took 3 mg before bed, I had good night sleep and joyful morning. Taking 10 mg before going to bed, gave me minor headache in the morning. In Europe, Melatonin is a prescription drug. In the U.S. you can buy it as a food additive.
Longevity substance number 3- Vitamin D. Similar to vitamin C, vitamin D is a highly potent antioxidant. Vitamin D has been shown to protect against various forms of cancer, and to extend the lifespan in laboratory animals. Recent studies in the Buck Institute for Research on Aging show that vitamin D engages longevity genes to increase lifespan and prvent the accumulation of toxic proteins linked to many age-related diseases.
Longevity substance number 4 - Acetyl-L-carnitine. There has been an explosion of publications about acetyl-l-carnitine for life extension. This is a modified amino acid compound which enters the blood stream and penetrates cell membranes more effectively than regular I-carnitine. Acetyl-l-carnitine is beneficial to heart muscle cells, the immune system, and probably enhances energy production in every cell of the body. The multi-faceted benefits of acetyl-l-carnitine in brain cells makes acetyl-l-carnitine the single most important supplement that we can take to maintain and improve overall neurological health. Acetyl-l-carnitine has been shown to improve neurological function even after we stop taking it, which suggests that acetyl-l-carnitine may re-program neuronal and neurotransmitter functions to enable the brain to function in a more youthful, energetic state. Healthy individuals are recommended to take at least two 50-day cycles (2 capsules each day) of acetyl-l-carnitine supplementation every year. If you can afford to take acetyl-l-carnitine more often, this should produce greater benefits.
Longevity substance number 5 - Deprenyl, also known as Eldepryl. Deprenyl is a potent inhibitor of MAO-B, the type of MAO that damages brain cells during normal aging. Taking Deprenyl results in dramatic life extension effects in animals. However, it appears that Deprenyl alone will not do as well in humans. In laboratory rats, the elevation of monoamine oxidase (MAO) plays a greater role in the aging process than in humans. Some patients take Deprenyl to help prevent Parkinson's disease and the symptoms of aging that are very similar to those suffered by Parkinson's patients. There is a substantial body of evidence, which suggests that Deprenyl protects many types of brain cells from premature aging and death. There is also evidence that Deprenyl boosts cellular production of SOD and catalase, the natural antioxidant enzymes that are depleted in aging. Typical protocol suggests 2-5 Deprenyl tablets (5 mg) a week for those in their 40s. The older you are, the more deprenyl you should take, but it is advisable not to take more than one 5-mg tablet (or capsule) of Deprenyl a day unless you have the early symptoms of Parkinson's or Alzheimer's disease. In this case, you should take 10 mg of Deprenyl a day under the supervision of a physician.
Longevity substance number 6 - Metformin. Metformin is an FDA approved first-line drug for the treatment of type 2 diabetes. Recently, FDA approved Metformin for extended studies on human subjects for its effect on lifespan extension. Metformin has been known for its beneficial effects on glucose metabolism. Evidence from animal models and in vitro studies suggest that in addition to its effects on glucose metabolism, Metformin may influence metabolic and cellular processes associated with the development of age-related conditions, such as inflammation, oxidative damage, diminished autophagy, and cell apoptosis. As such, Metformin is of particular interest in clinical translational research in aging since it may influence fundamental aging factors that underlie multiple age-related conditions. The investigators proposed a study to examine the effect of Metformin on the biology of aging in humans. Namely, whether treatment with Metformin will restore the gene expression profile of older adults with impaired glucose tolerance (IGT) to that of young healthy subjects. Metformin is a prescription drug.
Longevity substance number 7 - Phosphatidylserine (PS). There is a paradox: phosphatidylserine is sold as a drug in Europe at outrageously high prices, despite this is a phospholipid, which is easy and inexpensive to produce. Sunflower seeds and oil contain large amounts of phosphatidylserine. Fortunately, in the U.S. phosphatidylserine is available as a dietary supplement at reasonable prices. There is extensive evidence about the anti-aging benefits of phosphatidylserine. Phosphatidylserine may produce a cumulative effect that could enable people to reduce their dosage of the drug after attaining the desired cognitive enhancing benefits.
Longevity substance number 8 - Centrophenoxine. Longevity studies have documented anti-aging properties for the combination of DMAE and p-chlorophenoxyacetate. These two ingredients make up Centrophenoxine - a potent life-extension drug sold under several names, including Lucidril. Centrophenoxine has been shown to extend the lifespan of laboratory mice. It reduces a type of cellular debris called lipofuscin (aging pigment) in the neurons that populate our brain and central nervous system. The excessive accumulation of lipofuscin with advancing age has been linked to age-related neurologic diseases. Centrophenoxine speeds up information processing in the brain and enhances brain cell uptake of glucose. Brain cells use glucose to produce the energy they need to perform their neurological functions and to maintain cell viability. Some people cannot tolerate even one tablet a day of centrophenoxine, while others can take 1-4 tablets a day and experience dramatic cognitive and energy enhancing effects. Centrophenoxine is available from sources in Europe at affordable prices.
Longevity substance number 9 - GH3 and K.H.3. GH3 and K.H.3 are popular longevity compounds. Their active agent is procaine, an anti-aging drug discovered in the 1950s by Romanian physician Ana Asian. Both GH3 and K.H.3 suppress monoamine oxidase (MAO) levels. Elevated MAO destroys the essential neurotransmitters dopamine and norepinephrine. GH3 or KH3 also suppress elevated serum cortisol levels, which has been linked to several of the degenerative diseases of aging. GH3 and K.H.3 can be taken every day including the days you take Deprenyl, which is a selective MAO inhibitor. An appropriate dose of these drugs is one to two GH3 or KH3 tablets daily. Some doctors believe you should take a five day break from these drugs once a month to avoid too much monoamine oxidase suppression. However, the literature does not support the need for taking such a break.
Longevity substance number 10 - Piracetam. It is the most frequently used an offshore drug to boost short-term memory and overall cognitive function. There are more than 800 published studies documenting that Piracetam promotes youthful neurologic function, including enhanced cellular protein synthesis, interhemispheric and intercellular communication. Stroke victims might avoid paralysis, if given piracetam after entering the hospital. Even in patients who suffered stroke-induced brain cell injury years ago, there is evidence that piracetam may help to improve the functioning of these damaged cells. Piracetam is available in Europe.
Longevity substance number 11 - Human Growth Hormone. Growth hormone deficiency is a major reason for the decline in immune function and protein synthesis with aging in both muscle and neurologic tissues. Injections of synthetic human growth hormone have been used by geriatric physicians to rejuvenate aging men by increasing their muscle mass, strength, flexibility, and coordination. Recent studies suggest that growth hormone may be an effective treatment for the Alzheimer's disease and Parkinson's patients. Unfortunately, human growth hormone is artificially overpriced. The current cost of synthetic human growth hormone ranges from $12,000-225,000 annually, while its cost is $200-300/year. FDA restricts its sale in the United States. Producing synthetic growth hormone is as inexpensive as to synthesize insulin. Without FDA interference, most aging Americans could easily afford injections of growth hormone in an attempt to slow aging. The need to inject growth hormone also limits the availability of this highly potent life extension drug.
Fig. 1. Human body is encoded by ~25,000 genes, that produce ~2 million unique proteins, that, in turn, build ~10 trillion of our own cells. We share our body with ~10 trillion bacterial cells and ~100 trillion bacteriophage particles. The latter are viruses that infect bacteria.
Amazing design, isn’t it? The most amazing part is that this machinery functions properly most of the time!
Fig. 2. There are multiple dimensions of human body, numerous systems, subsystems, organs, tissues, and molecules that are related to, interact, and depend on each other. To simplify studies, scientists created distinct disciplines, such as genomics, proteomics, microbiomics, that systematically accumulate knowledge about, respectively, genes, proteins, microbes. Due to a number of reasons, certain areas, such as genomics, are at the present time in advanced state, in comparison with other areas, e.g. proteomics. Although genes encode, but proteins actually rule our body. Nucleic acids are more stable and robust compounds than amino acids that comprise proteins. For this reason genomics received abundant funding over the last decades, while proteomics and other “dimensions” still await the stage of explosive growth. Several areas are still in the stage of their infancy. One of them is the dimension of “subconscience.” The effects of placebo and nocebo occur in the dimension of subconscience. However, the mechanisms are still not clear.
Placebo and Nocebo. The effects of placebo and nocebo continue to bother my imagination. Think about the fact: on average 15% (up to 60% in the case of neurological drugs) respond to a placebo sugar pill as good as to real drugs. It means that placebo responders produce in their own bodies natural compounds that are as efficient as real drugs that almost always come with toxic side effects. This effect awaits careful attention and fundamental studies. I hope they will result in practical use of the placebo effect, at least by a portion of population, which is placebo-responsive. I guess, the factor of faith is an important constituent of the effect. If you do not trust, a sugar pill will not work. However, it is difficult to build a business around the effect of faith. We need a genius who will be capable to make money on placebo.
Nocebo is an even more powerful effect. On average 40% and in certain cases up to 65% of patients experience the nocebo effect. Nocebo is an effect of a sugar pill or harmless treatment that are administered to a patient and the patient is told that the pill is associated with undesirable or harmful side effects. The nocebo effect is an adverse reaction experienced by a patient, who receives such harmless therapy, but was told about possible side effects. Evidently, subconscious fears and negative expectations that are even more fundamental than trust, produce the effect similar to toxic drug. Similar effect is also well-known to medical students who discover in themselves many symptoms of a disease, which they study at the moment. This is one more example of our imagination and subconscience at play. Why wouldn’t we try to employ these phenomena for good purposes?
Low calories longevity - or calorie-restriction diet (without malnutrition ) has been shown to work in a variety of species, including yeast, fish, rodents, and dogs to decelerate the biological aging process, resulting in longer maintenance of youthful health and an increase in both median and maximum life-span. The life-extending effect of calorie restriction however is not shown to be universal. This effect appear to be related to reduced oxidative stress. It is an interesting topic to discuss.
Night sleep - as we know it plays important role in all aspects of our health. Not surprisingly, there is an important biological role of night sleep at the molecular level. Researchers from Columbia University recently discovered a dedicated vessel system and an amazing process, which resembles flushing the toilet. The flushing occurs only during our night sleep. During the day our brain operates intensely (at least in some of us, and at least sometimes)) and produces a lot of cellular and molecular debris. The debris must be flushed out before the next day begins. This is one more interesting topic to discuss and to employ for the extension of lifespan.