Total Internal Reflection Fluorescence
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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. 1. Human body consists of 10 trillion cells that are encoded by ~25,000 genes producing ~2 million unique proteins. We share our body with ~10-100 trillion bacterial cells and ~100-500 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.
The literature on longevity is enormous and rapidly growing. The recent progress is fantastic. Our children who are 20 and younger will have the opportunity to live 150-200 years or more. Unfortunately, not everyone will be capable of using this opportunity. It is not a trivial task to navigate in the ocean of longevity data. 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 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 i-Diagnostics will be an essential tool for longevity studies and individual longevity efforts. Using i-Diagnostics you will be able to design and fine tune individualized longevity program, which corresponds to unique set of properties of your body. However, you do not have to wait. You can start doing good things for your healthier life right now. The purpose of this webpage is to share with you our finding and thoughts. We would appreciate your feedback and comments sent to email@example.com.
We are interested in understanding the broad range of material interactions at different levels, especially at the level of the molecular mechanisms, since we are looking at molecular interactions in our research. However, the fantastically complex phenomenon of life cannot be reduced to the level of interactions between molecules. There is substantial body of evidence, which suggests that our mind, faith or fears can significantly affect our physiology and our biochemical reactions. It would be extremely exciting to study these dependencies and to utilize them for longevity studies. In this webpage, however, we focus on molecular aspects of aging.
Below, we will tell about our vision of the molecular aspects of aging. It is an extremely complex, multidimensional process, which we have only recently began to study at molecular level. We believe that life of a human being cannot be reduced to interactions between molecules, cells, tissues and organs. There are powerful dimensions of our minds, spirits, emotions, conscience and sub-conscience that via nervous and endocrine systems control our bodies. Our bodies consist of approximately 2 million unique proteins. 80% of 2 million build the nervous system. Great discoveries will be made in these areas. They will allow to increase the lifespan dramatically.
To initiate this discussion, we would like to share with our findings about the longevity drugs, substances, food additives, and lifestyle. We have analyzed the literature and other sources on the effects of different substances on longevity from the standpoint “First, do not harm” “Primum Non Nocere”- Hippocrates. We are ranking the longevity substances from the standpoint “First, Do Not Harm”. At the first place, they should not be toxic or harmful.
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. We are not sure about the percentage, but 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 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.
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.
i-Diagnostics for 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 our uniqueness is implemented at the molecular level.
Every one of us is truly unique. We respond differently to everything, including prescription and over-the-counter drugs. We have acquired sufficient knowledge to understand molecular mechanism and the diversity of these mechanisms. In scientific laboratories 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 i-Diagnostics, 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.
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. Good microbes will cooperate. In fact, they are so essential to our health that without them it is too difficult to keep our bodies 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. 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.
Top Eleven Longevity Drugs
Let us begin from the substances, including drugs. We ranked them in accordance with our own experience and 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, our experience showed discomfort of large doses. If we took 5 mg before bed, we had good night sleep and joyful morning. Taking 10 mg before going to bed, gave us 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 prevent 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.
Placebo and Nocebo Effects
The effects of placebo and nocebo continue to bother our imagination. Think about the fact: on average 15% (in the case of neurological drugs - up to 70%) respond to a placebo sugar pill as good as to a real drug. It means that placebo-responders (15% of volunteers) produce in their bodies natural compounds that are as efficient as real drugs. Remember, almost always drugs come with toxic side effects. Placebo effect awaits careful fundamental studies. I hope the studies will result in practical use of the placebo effect, at least by a portion of population, which is placebo-responsive. It appears that the factor of faith is an important constituent of the effect.
Nocebo is an even more powerful effect. 40-65% 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 belief, 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 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 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.