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 ====== Regenerative Medicine, Anti-Aging, Immortality ====== ====== Regenerative Medicine, Anti-Aging, Immortality ======
  
-On the subject of immortality. I have decided to go public as it seems to have stalled ​again, ​Hang on, I have little choice as I am out of the loop, the Illuminati'​s offer to reveal the secret to immorality comes with one condition, they could tell but they would have to kill me but seriously, charlatans and frauds occupy the space be it Harvard grape juice or the latest miracle nootropic, they have no human studies showing efficacy and likely not add a single day to life, like eBay turbo fans that claim 500% more horsepower they in fact hinder the horsepower. The latest answer to the French paradox is not "​150,​000,​000 glasses of wine (sic)"​. Two human trials of Nicotinamide Riboside (N.R) and Resveratrol concluded "The study found no clinical benefit to supplementation"​ Like many multi vitamins and other supplements it is [[science:​does_not_pass_through_the_small_intestine|rejected during the digestion process]] and does not pass into the bloodstream, a caution is the organs in charge of removing toxins ​can become damaged by abuse, over dose and over use of these tablets. Resveratrol is destroyed by sulfuric ​acid of the stomach and never enters the bloodstream,​ they know so but that does not stop them selling the rubbish. Every so often a new fad supplement comes about promising slow aging benefits like CoQ10, PQQ, Omega 3 but they soon fade away. Wrinkle creams we all know none are effective against wrinkles. Watch out for people who focus on some minor detail, ​aging is bigger than one drug, supplement or a special morning ritual. Buzzwords like anti-oxidants,​ anti-inflammatory or anti-aging, please this page is not about a fad lifestyle religion. Get real, move on... +On the subject of immortality. I have decided to go public as it seems to have stalledHang on, I have little choice as I am out of the loop, the Illuminati'​s offer to reveal the secret to immorality comes with one condition, they could tellbut they would have to kill me. But seriously, charlatans and frauds occupy the space be it Harvard grape juice or the latest miracle nootropic, they rarely ​have any studies showing efficacy and likely not add a single day to life but might take several away. The latest answer to the French paradox is not "​150,​000,​000 glasses of wine (sic)"​. Two human trials of Nicotinamide Riboside (N.R) and Resveratrol concluded "The study found no clinical benefit to supplementation"​ Like multi vitamins and other supplements it is [[science:​does_not_pass_through_the_small_intestine|rejected during the digestion process]] and does not pass into the bloodstream ​and their interference in the digestive system ​can lead to organ damage. Resveratrol is destroyed by sulphuric ​acid of the stomach and never enters the bloodstream,​ they know but that does not stop them selling the rubbish. Wrinkle creams have always been ineffective against wrinkles that does not stop them. Every so often a new fad supplement comes about promising slow aging benefits ​that cannot be ingored ​like CoQ10, PQQ, Omega 3 or a fruit with a fancy name, but they soon fade away. Aging is bigger than a minor detail, one drug, supplement or a special morning ritual. Get real, move on... 
  
 {{ ::​1-s2.0-s0092867413006454-gr1.jpg?​direct&​200|US vs Europe Pillars Of Aging}} {{ ::​1-s2.0-s0092867413006454-gr1.jpg?​direct&​200|US vs Europe Pillars Of Aging}}
 {{ ::​the-seven-pillars-of-aging.png?​direct&​200|US vs Europe Pillars Of Aging}} {{ ::​the-seven-pillars-of-aging.png?​direct&​200|US vs Europe Pillars Of Aging}}
-Getting old? What is getting old like? I do not have the same energy levels I did when I was young and their seems to be no way of endowing the body with energy. Food does not boost the energy, a good night sleep seems to be the only practice that improves energy levels modestly. The body seems sluggish, slow and limited to perform, more aches. The body differs in appearance from a young person and fat is impossible to remove. We may have all seen an end of life boxer step into the ring with a rising force and get beaten badly, yet that same boxer was unbeatable in his younger years. ​One way to describe is imagine a new 12v battery giving out 13.5v for a long period versus and old battery that maxes out at 11.5v and only for a short time. It can still perform all the functions of the new battery but at a reduced level of speed, power and durationWe want to get the battery back to holding 13.5v with its long and fast performance but their is none to turn the old battery back into a new batteryThe battery continues to degrade and finally ceases to functionNo nootropic, fruit juice will restore that battery function. Aging has many historical, artistic narratives such as the fountain of youth depicted in the movie cocoon where evil elderly humans drain the rejuvenating pool and kill the ancient cocooned aliens the pool was made to rejuvenate and so on, some Greek who was granted immortality on condition he could never have sex again, and so he decided to die (I just made that up but their is always one of those). Right: US 7 Pillars of Aging vs. Europe Pillars of Aging. ​Their are theories as to why aging occurs with two predominant theories ​of aging. Aging follows a biological timetable, perhaps a continuation of the one that regulates childhood growth and development. This regulation would depend on changes in gene expression that affect the systems responsible for maintenance,​ repair and defence responses ​and second theory are the damage or error theories emphasize environmental assaults to living organisms that induce cumulative damage at various levels as the cause of aging and eventually critical damage. ​As aging is complex both theories ​might collaberate ​to aging and death. Most people do not want to die but no one lives forever, natures 100% perfect strike rate, their is always an exception to the rule? no exceptions. Those that accept such become more mature and more human, mortal and weak. +Getting old? What is getting old like? I do not have the same energy levels I did when I was young and no way of endowing the body with energy. Food does not boost energy, a good night sleep seems to be the only practice that improves energy levels modestly. The body seems sluggish, tired, slow and limited to perform, more aches. The body differs in appearance from a young person and fat is impossible to remove. We may have all seen an end of life boxer step into the ring with a rising force and get beaten badly, yet that same boxer was unbeatable in his younger years. ​Read the [[https://​www.ncbi.nlm.nih.gov/​pmc/​articles/​PMC3836174/​|hallmarks of aging]]. Aging has many historical, artistic narratives such as the fountain of youth depicted in the movie cocoon where evil elderly humans drain the rejuvenating pool and kill the ancient cocooned aliens the pool was made to rejuvenate and many more, some Greek who was granted immortality on condition he could never have sex again, and so he decided to die (I made that up but there is always one of those). Right: US 7 Pillars of Aging vs. Europe Pillars of Aging. ​They are theories as to why aging occurs with two predominant theories. Aging follows a biological timetable, perhaps a continuation of the one that regulates childhood growth and development. This regulation would depend on changes in gene expression that affect the systems responsible for maintenance,​ repair and defence responses, secondly ​the damage or error theories emphasize environmental assaults to living organisms that induce cumulative damage at various levels as the cause of aging and eventually critical damage. ​Aging is complex ​but both theories ​are leading ​to genetic ​and epigenetics. Most people do not want to die but no one lives forever, natures 100% perfect strike rate, there is always an exception to the rule? No exceptions!
  
-Exception, in nature ​their is an example of immortality. Turritopsis dohrnii, the immortal jellyfish is able to revert completely to sexually immaturity, colonial stage after having reached sexual maturity ​as a solitary individual ​and theoretically,​ this process can go on indefinitely, ​effectively ​rendering the jellyfish biologically immortal. The Hyra and the Salamander have amazing regeneration ability, cut off its hand and it grows back. Lifespans; Arctica islandica and Ocean Quahog, shell fish both 500 years, Greenland shark 270 years, Bowhead Whales and Koi 200 years, ​ Galapagos Giant Tortoise 150 years (all the above live in the ocean) then their is a Tuataras a reptile 150 years, Elephants 70 years and Humans. The shortest lived animals, Gastrotrichs a marine microorganism 3 days, Drone Ants 3 weeks, Houseflies 4 weeks, House mouse 1 year, Chameleon 1 year, Guinea pigs 4 years, Domestic rabbits 8-12 years. Different animals have different lifespans ​and may suggest that lifespan is hardwired.+Exception, in nature ​there is an example of immortality. Turritopsis dohrnii, the immortal jellyfish is able to revert completely to sexually immaturity, colonial stage after having reached sexual maturity and theoretically,​ this process can go on indefinitely,​ rendering the jellyfish biologically immortal. The transformation might be epigenetic under the condition of starvation, sudden temperature change, reduction of salinity and damage to the bell. Scientists have attempted to isolate the action and genetically engineer transgenic human cells to be infused into humans. (Dimberu, Peniel M. (2011-04-25). "​Immortal Jellyfish Provides Clues for Regenerative Medicine"​. Singularity Hub. Retrieved 26 October 2011). What is left to do is find the genetic structure of immortality in the jellyfish and copy over to transgenic mice, it that works it could lead to a second type of Yamanaka like factors. The Hydra and the Salamander have amazing regeneration ability, cut off its hand and it grows back. Lifespans; Arctica islandica and Ocean Quahog, shell fish both 500 years, Greenland shark 270 years, Bowhead Whales and Koi 200 years, ​ Galapagos Giant Tortoise 150 years (all the above live in the ocean) then there is a Tuataras a reptile 150 years, Elephants 70 years and Humans. The shortest lived animals, Gastrotrichs a marine microorganism 3 days, Drone Ants 3 weeks, Houseflies 4 weeks, House mouse 1 year, Chameleon 1 year, Guinea pigs 4 years, Domestic rabbits 8-12 years. Different animals have different lifespans ​suggesting ​lifespan is hardwired.
  
-General health, the whole goal is staying pre-clinical for as long possible by healthy practices. ​The longest ​living ​people and possibly the healthiest tend to live around islands namely Sardinia, Okinawa and Santorino. The water purifies the air and benefits both lungs and body. The water is high quality and the clean air and water means the food is better quality all of which lead to a longer life. Wealthy people also tend to live longer due to better conditions. In contrast, the west is hell bent on contaminating ​its environment with exhausts and chemicals, the air is not cleanneither is the water and the food is not fit for human consumption and people breathe smoke into their lungs along with many other disastrous practices. Clean environments that promote health aid in longer life and health span. Health and life span has developed using evolution and evolution explains many of the mechanisms ​we use to explain why some activity might be healthy or unhealthy. Learning to live a healthy lifestyle, the best nutritional advice is not to eat at all or fasting, the body works on air and water and very much less on food. Do cardio and weight training, secure good quality air and water and many other practices such living close to the ocean, getting some sun minus the U.V, walking barefoot on the sand, sleeping practices buy the highest quality mattress you can afford and so on. If one cannot add days to life, then optimize lifestyle through how we use our time and how we treat the body. Some people limit their sleep to have more time, move relative to climate to gain more usable days and so on. Do not discount the placebo effect as it is no small or insignificant statistical aberration, estimates of the placebo cure rate range from a low of 15 percent to a high of 72 percent. The longer the period of treatment and the larger the number of physician visits, the greater the placebo effect. Try to activate the placebo effect in your lifestyle. However, ​their are many practices that people push but in reality will not stop aging, the bodies intent to age requires more powerful action.+The longest ​lived people and possibly the healthiest tend to live around islands namely Sardinia, Okinawa and Santorino. The water purifies the air and benefits both lungs and body. The water is high quality and the clean air and water means the food is better quality all of which lead to a longer life. Wealthy people also tend to live longer due to better conditions. In contrast, the west is hell-bent on contaminating ​the environment with exhausts and chemicals, the air is not clean and neither is the waterthe food is not fit for human consumption and people breathe smoke into their lungs along with many other disastrous practices. Clean environments that promote healthaid in longer life and health span. Health and life span has developed using evolution and evolution explains many of the mechanisms ​used to explain why some activity might be healthy or unhealthy. Learning to live a healthy lifestyle, the best nutritional advice is not to eat at all or fasting, the body works on air and water and very much less on food. Do cardio and weight training, secure good quality air and water and many other practices such living close to the ocean, getting some sun minus the U.V, walking barefoot on the sand, sleeping practices buy the highest quality mattress you can afford and so on. If one cannot add days to life, then optimize lifestyle through how we use our time and how we treat the body. Some people limit their sleep to have more time, move relative to climate to gain more usable days and so on. Do not discount the placebo effect as it is no small or insignificant statistical aberration, estimates of the placebo cure rate range from a low of 15 percent to a high of 72 percent. The longer the period of treatment and the larger the number of physician visits, the greater the placebo effect. Try to activate the placebo effect in your lifestyle. However, ​there are many practices that people push but in reality will not stop aging, the bodies intent to age requires more powerful action. Think general health, the whole goal is staying pre-clinical for as long possible by healthy practice
  
-Free radicals, oxidative stress. A major theory of aging is the free radicals theory or aging. The free radical theory of aging states ​that organisms age because cells accumulate free radical damage over time. A free radical is any atom or molecule that has a single unpaired electron in an outer shell. It is believed that over 90 diseases are related ​to oxidative stress. ​The assumption is electrons in your body come from food and can only be derived from food "​anti-oxidants"​ but that is not the reality. Electrons ​are everywhereAntioxidant pills and foods have become a way to market substances that have no real health benefit instead simply walk barefoot at the park, bathe in the ocean. When you electrically earth the body, electrons pass through. The most effective way of gaining electrons is by electrically earthing the body overnight. An earthing mattress is a mattress that at one point emits electrons and at the other point Earths the bodya person sleeps on the bed overnight and during ​that time electrons pass through the body and into the Earth fixing oxidative stress. Spending eight hours each night should not only treat the causes of these reactive species but also supply mitochondria extra electrons for energy, i.e. supplying the body with extra electrons while also earthing the body during sleep should have a major effect on health and energy as electrons are the source of energy in the body. Earthing mattress or pads are easily sourced ​but adding ​an electron ​generator or emitter ​unproven ​might supercharge the therapy. The mattress simply plugs into a power outlet. The earth contains electrons and the moment you touch earth at the speed of light all the atoms in your body are neutralizedStudy [[https://​www.ncbi.nlm.nih.gov/​pmc/​articles/​PMC3265077|Earthing:​ Health Implications of Reconnecting the Human Body to the Earth'​s Surface Electrons]] ​(no products required). ​[[https://ganino.com/doco.php?a=Antioxidants Free Radicals|Antioxidants and Radicals]] \\+[[https://​ganino.com/​doco.php?​a=Antioxidants Free Radicals|Free radicals, oxidative stress]]. A major theory of aging is the free radical theory of aging, stating ​that organisms age because cells accumulate free radical damage over time. A free radical is any atom or molecule that has a single unpaired electron in an outer shell. It is believed that over 90 diseases are attributed ​to oxidative stress. ​However, the assumption is electrons in the atoms that form your body come from food and can only be derived from food "​anti-oxidants"​ but that is not the case and food is not the highest source of antioxidants,​ electrons ​are everywhereAntioxidant pills and foods have become a way to market substances that have no real health benefit instead simply walk barefoot at the park, bathe in the ocean or sleep grounded. When you electrically earth the body, electrons pass through. The most effective way of gaining electrons is by electrically earthing the body overnight, ​as you sleep you double use that time to get a health benefit. Spending eight hours each night should not only treat the causes of these reactive species but also supply mitochondria extra electrons for energy, i.e. supplying the body with extra electrons while also earthing the body during sleep should have a major effect on health and energy as electrons are the source of energy in the body. Earthing mattress or pads are easily sourced, it is about surface area, how much of your skin is touching earth. While not required perhaps ​adding ​small electron emitter might supercharge the therapy ​more (not proven, I just made that up). The mattress ​sheets ​simply plugs into a power outlet. The earth contains electrons ​naturally ​and the moment you touch earth you normalize ​the atoms in your body, if you need more electrons the Earth sends it up to you, if you have too many the Earth takes it backA multimeter can be used to test grounding effectiveness of any modication by putting the meter on AC and putting the negative in earth and holding the positive. Earthing like gym excercise is not done constantly, the benefits cover you outside of the practice, every night. Z potential. Studies: ​[[https://​www.ncbi.nlm.nih.gov/​pmc/​articles/​PMC3265077|Earthing:​ Health Implications of Reconnecting the Human Body to the Earth'​s Surface Electrons]][[https://www.ultimatelongevity.com/earthing-grounding/​the-research.shtml?ref=56|Earthing Grounding The Scientific Research]], [[https://​www.ncbi.nlm.nih.gov/​pmc/​articles/​PMC3576907/​|Earthing (Grounding) the Human Body Reduces Blood Viscosity—a Major Factor in Cardiovascular Disease]], [[https://​newatlas.com/​medical/​gut-molecules-early-death-sleep-deprivation/​|Gut molecules implicated in early death from sleep deprivation]].
  
 Rapamycin and Metformin, two touted drugs with the potential to increase human lifespan both target mTOR (mammalian target of rapamycin). Their are no human studies showing efficacy as of mid 2020. mTor is further divided into mTor1 and mTor2 each group separate process. mTor is a growth regulator in relation to available nutrients and when mTor growth regulation is suppressed perhaps during puberty the organism grows to its maximum regardless of available nutrients. Metformin (a diabetes drug) is believed to mimic the benefits of exercise in a pill without any exercise ;-) AMPK activation while Rapamycin (immune-suppressant drug) is believed to trigger autophagy something that occurs after fasting for 16 hours, autophagy improves cellular condition and the condition of every aspect of the cell is super important for health. Both these drugs have side effects with Rapamycin believed to be a weekly or twice a month drug with daily use being life-shortening and Metformin having no gain in people without Type 2 diabetes. Sestrins (Sesns) are groups of proteins made when a person excercises, accumulate in the muscle and so the possibility of "​eating"​ (big molecules not bioavailable) the proteins to mimic excercise. Stress-induced Sesn expression results in inhibition of the target of rapamycin complex 1 (TORC1). Rapamycin and Metformin, two touted drugs with the potential to increase human lifespan both target mTOR (mammalian target of rapamycin). Their are no human studies showing efficacy as of mid 2020. mTor is further divided into mTor1 and mTor2 each group separate process. mTor is a growth regulator in relation to available nutrients and when mTor growth regulation is suppressed perhaps during puberty the organism grows to its maximum regardless of available nutrients. Metformin (a diabetes drug) is believed to mimic the benefits of exercise in a pill without any exercise ;-) AMPK activation while Rapamycin (immune-suppressant drug) is believed to trigger autophagy something that occurs after fasting for 16 hours, autophagy improves cellular condition and the condition of every aspect of the cell is super important for health. Both these drugs have side effects with Rapamycin believed to be a weekly or twice a month drug with daily use being life-shortening and Metformin having no gain in people without Type 2 diabetes. Sestrins (Sesns) are groups of proteins made when a person excercises, accumulate in the muscle and so the possibility of "​eating"​ (big molecules not bioavailable) the proteins to mimic excercise. Stress-induced Sesn expression results in inhibition of the target of rapamycin complex 1 (TORC1).
  
-Sirtiuns are a class of proteins that possess either mono-ADP-ribosyltransferase,​ or deacylase activity, including deacetylase,​ desuccinylase,​ demalonylase,​ demyristoylase and depalmitoylase activity. Sirtuins regulate important biological pathways in bacteria, archaea and eukaryotes. The attempt to activate situins, promote biogenesis / homeostasis in Mitochrondria,​ responsible for giving energy to cells. Sirtuin, Sirt 1,​2,​3,​4,​5,​6,​7 are a class of proteins responsible for metabolism, cell cycle, DNA repair and rRNA transcription. Their are no known drugs that can trigger for example DNA repair. Poly (ADP-ribose) polymerase (PARP) is a family of proteins involved in a number of cellular processes such as DNA repair, genomic stability, and programmed cell death.+Sirtiuns are a class of proteins that possess either mono-ADP-ribosyltransferase,​ or deacylase activity, including deacetylase,​ desuccinylase,​ demalonylase,​ demyristoylase and depalmitoylase activity. Sirtuins regulate important biological pathways in bacteria, archaea and eukaryotes. The attempt to activate situins, promote biogenesis / homeostasis in Mitochrondria,​ responsible for giving energy to cells. Sirtuin, Sirt 1,​2,​3,​4,​5,​6,​7 are a class of proteins responsible for metabolism, cell cycle, DNA repair and rRNA transcription. Their are no known drugs that can trigger for example DNA repair. Poly (ADP-ribose) polymerase (PARP) is a family of proteins involved in a number of cellular processes such as DNA repair, genomic stability, and programmed cell death. STACs (small molecule sirtuin activators) are drugs for sirt activation.
  
-Nicotinamide adenine dinucleotide,​ NAD+ a cofactor that is central to metabolism. Many proteins decrease with age and some increase, NAD+ is produced by the liver and said to decrease in production with age. Low levels of NAD+ are said to decrease sirtiun or parp activity, acetylation and lifespan. People who supplement with NAD+ or a precursor generally feel no benefit, do not appear more youthful and have a placebo effect outlook. It is said that without NAD+ you would die, what does that even mean? If I don'​t ​intake air and water would also die and does that mean I should ​breathe more air and drink more water and I become younger or age better? You are going to blow noxious gas all day out the exhaust, pollute the drinking water with all sorts of heavy metals and toxins then breathe in that polluted air and drink that water then push research into sugar pills for health reasons? ​Another important information to consider is that when people supplement the organ that normally produces that supplement loses its ability to do so. Such as people who supplement with testosterone,​ their testicles shrink as it no longer produces the hormone, supplementing with NAD+ may cause the same situation. In aged people this may cause low NAD+ levels for more than a year or more after it is stopped, their are also methylation deficiency that arise from supplementation. This leads to a very important question, why? Does it decrease with age and how is it remedied without supplementation. A much more difficult problem to solve. NAD+ fad supplementation is probably a scam. +Nicotinamide adenine dinucleotide,​ NAD+ a cofactor that is central to metabolism. Many proteins decrease with age and some increase, NAD+ is produced by the liver and said to decrease in production with age (almost every measure does with age). Low levels of NAD+ are said to decrease sirtiun or parp activity, acetylation and lifespan. People who supplement with NAD+ or a precursor generally feel no benefit, do not appear more youthful and have a placebo effect outlook. It is said that without NAD+ you would die, what does that even mean? If you removed a persons liver or blood they would also die, if you do not intake air and water you would also die, rather than breathe more air and drink more water instead ​blow noxious gas all day out the exhaust, pollute the drinking water with all sorts of heavy metals and toxins then breathe in that polluted air and drink and ignoring all that sell pills. NMN is not bioavailable and N.R does not make it past the digestive system. It is also a complex process, dumping substances into the bloodstream is too simplistic as their are myriad of domino effects. ​Another important information to consider is that when people supplement the organ that normally produces that supplement loses its ability to do so, dystrophy. Such as people who supplement with testosterone,​ their testicles shrink ​(hypogonadism) ​as it no longer produces the hormone, supplementing with NAD+ may cause the same situation. In aged people this may cause low NAD+ levels for more than a year or more after it is stopped ​secretly creating an addiction cycle, their are also methylation deficiency that arise from supplementation. This leads to a very important question, why? Does it decrease with age and how is it remedied without supplementation. A much more difficult problem to solve. NAD+ fad supplementation is probably a scam. Niacin, Vitamin B3 is a cheap yet equal substitute for expensive N.R
  
-Telomeres, ​their was that whole telomeres humdrum a while back. Telomeres are the strands at the end of DNA when they decrease in length aging accelerates. The body naturally produces telomerase to maintain telomeres but attempts to increase telomeres artificially using telomerase causes cancer. Danazol may or may not be able to lengthen telomeres but has many side effects but generally not a cancer causing agent. ​Active ingredient ​Cycloastragenol is a molecule isolated from various species in the genus Astragalus that is purported to have telomerase activation activity. A single in vitro study on human CD4 and CD8 T cells led to claims that cycloastragenol may activate telomerase, leading to controversial claims for its role in reducing the effects of aging. However, ​this product should not be taken as their are reports of liver cancer. It is believed that cancer ​is a concern for the body and billions of cells are apoptose ​and replaced each day to avoid cell dysfunction including cancer. Dyskeratosis congenita (DKC), also known as zinsser-engman-cole syndrome is characterized by short telomeres. Some of the manifestations resemble premature aging (similar to progeria), it might be caused by a gene mutation inhibiting telomerase production.+Telomeres ​(Blackburn, Greider)there was that whole telomeres humdrum a while back. Telomeres are the strands at the end of DNA when they decrease in length aging accelerates. The body naturally produces telomerase to maintain telomeres but attempts to increase telomeres artificially using telomerase causes cancer. If a cell has DNA damage and short telomeres, extending the telomeres causing the cell to replicate multiplies the DNA damage which is very bad, cancer level bad. Teleomere shortening with cell division may then be a way to limit the cell relative to damage. Danazol may or may not be able to lengthen telomeres but has many side effects but generally not a cancer causing agent. Cycloastragenol is a molecule isolated from various species in the genus Astragalus that is purported to have telomerase activation activity. A single in vitro study on human CD4 and CD8 T cells led to claims that cycloastragenol may activate telomerase, leading to controversial claims for its role in reducing the effects of aging. However, ​there are reports of liver cancer. It is believed that in an effort to avoid cancer and other dysfunction ​billions of cells are apoptosed ​and replaced each day. Dyskeratosis congenita (DKC), also known as zinsser-engman-cole syndrome is characterized by short telomeres. Some manifestations resemble premature aging (similar to progeria), it might be caused by a gene mutation inhibiting telomerase production. Telomeres are one aspect of many aged cell morphology issues, a protocol must be particular about the many aspects of a cell's condition prior to extending telomeres.
  
-Cdc42, ​when any cell in the body needs replacing it most likely will come from your own haematopoietic stem cells, ​as the bodies ​haematopoietic ​stem cells generation factory ages they come functional yet degraded from the beginning. Cdc42 activity regulates haematopoietic stem cell aging and rejuvenation. Department of Dermatology and Allergic Diseases, University of Ulm, 89091 Ulm, Germany. The decline in haematopoietic function seen during aging involves a progressive reduction in the immune response and an increased incidence of myeloid malignancy, and has been linked to aging of haematopoietic stem cells (HSCs). The molecular mechanisms underlying HSC aging remain unclear. In their paper they demonstrate that elevated activity of the small RhoGTPase Cdc42 in aged HSCs is causally linked to HSC aging and correlates with a loss of polarity in aged HSCs. Pharmacological inhibition of Cdc42 activity functionally rejuvenates aged HSCs, increases the percentage of polarized cells in an aged HSC population, and restores the level and spatial distribution of histone H4 lysine 16 acetylation to a status similar to that seen in young HSCs. Their data suggests a mechanistic role for Cdc42 activity in HSC biology and epigenetic regulation, and identify Cdc42 activity as a pharmacological target for ameliorating stem cell aging.+Cdc42, ​bone marrow derived stem cells, ​haematopoietic stem cells and mesenchymal stem cells (multipotent stromal cells that can differentiate into a variety of cell typesincluding osteoblasts (bone cells), chondrocytes (cartilage cells), myocytes (muscle cells) and adipocytes (fat cells which give rise to marrow adipose tissue)). As the bodies stem cell generation factory ages they come functional yet degraded from the beginning. Cdc42 activity regulates haematopoietic stem cell aging and rejuvenation. Department of Dermatology and Allergic Diseases, University of Ulm, 89091 Ulm, Germany ​[[https://​pubmed.ncbi.nlm.nih.gov/​22560076/​|1]],​[[https://​pubmed.ncbi.nlm.nih.gov/​24141946/​|2]]. The decline in haematopoietic function seen during aging involves a progressive reduction in the immune response and an increased incidence of myeloid malignancy, and has been linked to aging of haematopoietic stem cells (HSCs). The molecular mechanisms underlying HSC aging remain unclear. In their paper they demonstrate that elevated activity of the small RhoGTPase Cdc42 in aged HSCs is causally linked to HSC aging and correlates with a loss of polarity in aged HSCs. Pharmacological inhibition of Cdc42 activity functionally rejuvenates aged HSCs, increases the percentage of polarized cells in an aged HSC population, and restores the level and spatial distribution of histone H4 lysine 16 acetylation to a status similar to that seen in young HSCs. Their data suggests a mechanistic role for Cdc42 activity in HSC biology and epigenetic regulation, and identify Cdc42 activity as a pharmacological target for ameliorating stem cell aging. (immuno-decline and pericyte activation). The prospect that HSCs and even MSCs could be kept very young. This bone marrow stem cell production system is important in aging. ​
  
-Clearing senescent cellsdamaged cells that stop dividingcalled senescent cells, accumulate ​with ageand are thought to contribute to inflammation,​ tissue damage and age-related diseases. ​A peptide that impairs binding between ​the proteins FOXO4 and p53 — an interaction that normally inhibits the '​self-destruct'​ signal ​in senescent cells. ​Their are some drugs named senolytic drugs that are able to clear senescent cells allowing ​new cells can take their place. Good house keeping? ​We require more kinds of senolytics, ​against cancer, ​cancer prevention, scar tissue removal and so on. For example, if a senolytic could target detect and only destroy cells with short telomeres, ​one injection could be cancer prevention treatment or if it could detect and destroy only scar tissue it could be a scar tissue removal treatment and so on. The deleted senescent cell are replaced as part of the bodies natural process ​where the opportunity ​with for example cdc42 to replace with higher quality ​cell.+Clearing senescent cells. Senescent cells are damaged cells that are in a cell cycle arreststopped from replicating but resident. Accumulate ​with age and are thought to contribute to inflammation,​ tissue damage and age-related diseases. ​Senescent cells remove themselves or are removed by the immune system. Immune system decline with age leads to accumulation of senescent cells, immune system cell types are made in the body and form part of blood composition. Senescent cells secret ​senescent ​factors. Senescent associated secretory phenotype (SASP), the increased expression and secretion of a suite of inflammatory cytokines, chemokines, growth factors, and proteases (Coppé et al., 2010a; van Deursen, 2014). Senescent ​cells are believed to be a cell state for tumour suppression,​ while fine in the young body, they compound aging in aging bodiesThere are some drugs named senolytic drugs that claim to clear senescent cellsnew cells are formed in their place. Good house keeping? ​Drugs that target those mechanisms have been shown to clear up to 50% of senescent cells from aged tissues, the actual amount varying widely by tissue and drug type - in some tissues, the effect is negligible for the drugs tried to date. More types of senolytics ​are requiredfor cancer ​treatment and prevention, scar tissue removal and so on, even pre-senolytic,​ anticipating cells that are showing first stages of damage. We also know that senescent cells occur in the brain so a senolytic that crosses the blood brain barrier. For example, if a senolytic could target detect and only destroy cells with short telomeres, ​an injection could be an effective ​cancer prevention treatment or if it could detect and destroy only scar tissue it could be a scar tissue removal treatment and so on. The deleted senescent cell are replaced as part of the bodies natural process ​either when an adjacent cell divides or from bone marrow derived pericyte stem cell. These cells must be replaced with better cells and so an optimal replacement cell protocol is also required. Methods; FOXO4-related peptides. FOXO4 can bind with p53 protein to induce cellular senescence, A peptide that impairs binding between ​the proteins FOXO4 and p53 — an interaction that normally inhibits the '​self-destruct'​ signal in senescent cells. Recent study in which researchers killed senescent cells by interfering in the crosstalk between FOXO4 and P53 reported an SI50 (selectivity index - the effectiveness index for senolytics) about 12. Inhibitors of different members of the bcl-2 family of anti-apototic proteins. Inhibitors of USP7 ([[ubiquitin_excercise|Ubiquitin]]-specific processing protease 7). Senolytic agents studied previously, including dasatinib, quercetin and ATTAC, did not include measurements of SI50. Typical drug protocol senolytic drugs Dasatinib + Quercertin twice annually (not pills instead injections). Not one senoltyic is effective against every type of senescent cell in the human body, opting for the strategy of a combination or cocktail of senolytics ​with their individual target method. Also, one injection has shown to be effective ​for up to 7 months, evidence for an easy bi-annual injection treatment. There is also the group that is working on T-cells or Killer cells as senolytic. Humans are made up of a variety of different cells, all of which are different sizes, shapes and have different functions. The average size of a human cell is between 10 and 100 micrometers.It also leads us to assume that the daily dose pills already on sale in the vitamin section of the local stores sold as senolytics are fake products. Article: [[https://​age-reversal.net/​dr-jerry-mixon-case-study/​|Using senolytics prior to stem cell infusion may or may not enhance the treatment]],​ [[https://​www.ncbi.nlm.nih.gov/​pmc/​articles/​PMC5641223/​|The Clinical Potential of Senolytic Drugs]], [[https://​www.ncbi.nlm.nih.gov/​pmc/​articles/​PMC1905691/​|Ageing,​ tumour necrosis factor-alpha (TNF-α) and atherosclerosis]],​ [[https://​pubmed.ncbi.nlm.nih.gov/​31838837/​|Senolytics and Senostatics:​ A Two-Pronged Approach to Target Cellular Senescence for Delaying Aging and Age-Related Diseases]]
  
-Hypothalamus,​ the hypothalamus starts and ends puberty, initiates body changes for pregnancy and initiates ​menopause and the gland also knows how to keep time, the circadian rhythm or day/night cycle is in the hypothalamus. This small gland in the brain is believed to keep time for an organism'​s lifespan. It also exists in the most ancient part of the brain called the limbic system, circadian rhythms exists in every animal and plants. When the hypothalamus senses low oestrogen in the blood of a woman it sends a signal to the pituitary gland which in turn sends a signal to the ovaries to produce more oestrogen, in males that dope on testosterone or steroids cause dystrophy to their testicles because the hypothalamus sensing adequate levels of testosterone will not require the testicles to produce testosterone. ​It is the hypothalamus that decides if a woman is pre and post menopausal and then sets the specific regulation ​of oestrogen levels ​which suggests that gene expression ​is being regulated by lifespan time keeping mechanism in the hypothalamus. That the circadian rhythm is in the hypothalamus makes the organ highly suspicious of being in part the timer for lifespan. The master clock of the human body is called the (SCN) Suprachiasmatic nucleus consisting of 20,000 neurons, time keeping systems like these in the central nervous system are believed to be dictating the lifespan of an organism. In this case averting death is similar to attempting to avoid puberty, regardless of what you do sooner of later it is going to happen. Centenarians persons that live up to and past 100 years run in families and different animals have their specific lifespan both suggest genetic lifespan mechanism ​and that mechanism may be a group of neurons in the brain keeping time. Depending on the time parts of the genome are expressed while other parts are no longer expressed. Researchers at Albert Einstein College of Medicine conducted a study on mice. They discovered that as mice age, levels of molecules, specifically IKK-β and NF-kB, molecules that initiate inflammatory responses, increase in the brain, particularly in the hypothalamus. The concentration of the pro inflammatory cytokine ​tumor necrosis factor β also increases. The increases directly cause a decline in gonadotropin-releaseing hormone (GnRH). Mice that produced less IKK-β and NF-kB in the hypothalamus created more neurons and solved mazes more quickly, had greater muscle strength, and exhibited a 20% longer lifespan. The opposite effects were seen in mice that overproduced IKK-β and NF-kB. +Hypothalamus,​ the hypothalamus ​controls child growth phase, ​starts and ends puberty, initiates body changes for pregnancy and menopause and the gland also knows how to keep time, the circadian rhythm or day/night cycle is in the hypothalamus. This small gland in the brain is believed to keep time for an organism'​s lifespan. It exists in the most ancient part of the brain called the limbic system. When the hypothalamus senses low oestrogen in the blood of a woman it sends a signal to the pituitary gland which in turn sends a signal to the ovaries to produce more oestrogen, in males that dope on testosterone or steroids cause dystrophy to their testicles because the hypothalamus sensing adequate levels of testosterone will not require the testicles to produce testosterone. ​Puberty occurs with clockwork regularity, ​the method ​and control ​of which is unknown, perhaps it is neural clock perhaps accumulation of methylation act as a clock, telomeres are a type of cell division clock. That the circadian rhythm is in the hypothalamus makes the organ highly suspicious of being in part the timer for lifespan, such a master clock of the human body is called the (SCN) Suprachiasmatic nucleus consisting of 20,000 neurons, time keeping systems like these in the central nervous system are believed to be dictating the lifespan of an organism. In this case averting death is similar to attempting to avoid puberty, regardless of what you do sooner of later it is going to happen. Centenarians persons that live up to and past 100 years run in families and different animals have their specific lifespan both suggest genetic lifespan mechanism. Depending on the time parts of the genome are expressed while other parts are no longer expressed. The strategy of the hypothalamus is one organ has major importance to aging while other have minor importance. What happens at the important organ goes systemic and the effect cascades or it has a domino effect throughout the body. The endocrine system with the hypothalamus being number one and the pituitary gland number two. Researchers at Albert Einstein College of Medicine conducted a study on mice. They discovered that as mice age, levels of molecules, specifically IKK-β and NF-kB, molecules that initiate inflammatory responses, increase in the brain, particularly in the hypothalamus. The concentration of the pro inflammatory cytokine ​tumour ​necrosis factor β also increases. The increases directly cause a decline in gonadotropin-releaseing hormone (GnRH). Mice that produced less IKK-β and NF-kB in the hypothalamus created more neurons and solved mazes more quickly, had greater muscle strength, and exhibited a 20% longer lifespan. The opposite effects were seen in mice that overproduced IKK-β and NF-kB. Zhang G et al. Hypothalamic programming of systemic ageing involving IKK-β, NF-kB and GnRH. Nature 2013 May 9; 497:211. Gabuzda D, Yankner BA. Physiology: Inflammation links ageing to the brain. Nature 2013 May 9; 497:197. [[https://​www.sciencedaily.com/​releases/​2017/​07/​170726132107.htm|Brain cells found to control aging]], Yalin Zhang, Min Soo Kim, Baosen Jia, Jingqi Yan, Juan Pablo Zuniga-Hertz,​ Cheng Han, Dongsheng Cai. Hypothalamic stem cells control ageing speed partly through exosomal miRNAs. Nature, 2017; DOI: 10.1038/​nature23282.
-Zhang G et al. Hypothalamic programming of systemic ageing involving IKK-β, NF-kB and GnRH. Nature 2013 May 9; 497:211. Gabuzda D, Yankner BA. Physiology: Inflammation links ageing to the brain. Nature 2013 May 9; 497:197+
  
-Trans-humanism,​ biomedical engineering,​ replacing many parts of the body with "​superior"​ mechanical prosthetics. Improving prosthetic technology has noble medical applications ​either way, the key is fusing bio with the mechanical. ​Not growing a new bio liver with stem cells, ​but being able to make such organs and limbs mechanically and have them perform to the same standard. Their are issues with the complexity of the human body causing the prosthetic to be always unsatisfactory. People want an arm, hand and fingers that are identical to their biological version in every way. From the effortless control of the limb to its dexterity and if it falls short ever so slightly ​then it fails completely. Eventually only the head will remain and then only the brain and so on. The whole head transplant, ​organ transplant system ​has to fade into history and that chapter closed. ​The major issue is that when a person loses an arm or a leg hospital duration is 6 months and rehabilitation takes years and also modern prosthetics are still not ideal. The advantage is that metal lasts a very long time and is simpler than the body limb, living on Mars or on the Moon becomes applicable as no oxygen is required and the materials can handle the harsh environments. How to make Voltron? Call four sexy friends "Form Voltron, activate interlock, Go Voltron Force" I prefer Mighty Morphin'​ Power Rangers. Oh, continue reading...+Trans-humanism,​ biomedical engineering,​ replacing many parts of the body with "​superior"​ mechanical prosthetics. Improving prosthetic technology has noble medical applications ​even if it does not yield any more advantages, the key is fusing bio with the mechanical. ​Their are those that are attempting to grow new bio liver with stem cells, ​while this is being able to make such organs and limbs mechanically and have them perform to the same standard. Their are issues with the complexity of the human body causing the prosthetic to be always unsatisfactory. People want an arm, hand and fingers that are identical to their biological version in every way. From the effortless control of the limb to its dexterity and qualifying expectations, ​if it falls short then it fails completely. Eventually only the head will remain and then only the brain and so on. The head transplant ​experiment a while back is not feasible, plagued with too many issues, has to fade into history and that chapter closed. ​Their is the effort to build organs using the recipients own stem cells which avoid rejection issues. Humans download their brain to a mainframe, they will exist virtually until a clone is made and the technology exists to download the virtual self back into the clone. Cryogenics is freezing oneself and then unfreezing oneself after a time, Their is no way to unfreeze them at this stage so I do not think this can work. Back to transhumanism,​ the major issue is that when a person loses an arm or a leg hospital duration is 6 months and rehabilitation takes years. The advantage is that metal lasts a very long time and is simpler than the body limb, living on Mars or on the Moon becomes applicable as no oxygen is required and the materials can handle the harsh environments. How to make Voltron? Call four sexy friends "Form Voltron, activate interlock, Go Voltron Force" I prefer Mighty Morphin'​ Power Rangers. Oh, continue reading ​then...
  
-It is believed that aging is genetic at its source and gene therapy is the means to extend life. CRISPR-Cas9,​ a DNA editing ​tool where the Cas9 protein cuts the DNA and new DNA is inserted. Sometimes the protein cuts and inserts in the wrong place. The effect of changing DNA randomly is massive haemorrhage,​ massive inflammation and death within a week. However, their are many animals that have been successfully altered with the technology such as mice and cats that glow in the dark and so on. Of course this whole [[genetic_engineering|genetic ​engineering]] ​field effects all living creatures and even plants. Corporations want to alter the seed of a plant so that it does not re-produce leaving them monopoly sole supplier of the seed, an act considered pure evil and potentially dangerous that an Arctic seed vault had to be constructed see GMO.+It is believed that aging is genetic at its source and gene therapy is the means to extend life. Just say "CRISPR-Cas9" as if it magically solves eveything, CRISPR, a DNA editing ​system ​where the Cas9 protein cuts the DNA so new DNA can be inserted. Sometimes the protein cuts and inserts in the wrong place. The effect of changing DNA randomly is massive haemorrhage,​ massive inflammation and death within a week. However, their are many animals that have been successfully altered with the technology such as mice and cats that glow in the dark and so on. Our application requires highly controlled systemic or organ specific genetic therapy which is not currently available with any vector. ​[[genetic_engineering|Genetic ​engineering]] effects all living creatures and even plants. Corporations want to alter the seed of a plant so that it does not re-produce leaving them monopoly sole supplier of the seed, an act considered pure evil and so potentially dangerous that an Arctic seed vault, Svalbard Global Seed Vault had to be constructed, evil people do really exist. ​see GMO.
  
 {{ ::​progeria.png?​direct|}} {{ ::​progeria.png?​direct|}}
  
-The difference being male or female is said to be the instructions within the XX chromosome or the XY chromosome. The male produces both types, when the specific gene is read the instruction is a boy or a girl. Some reptiles have an environmental determinate,​ for example hot outside, a male versus cold outside, a female. This illustrates epigenetics and the powerful machine of genetics. One theory of aging is that as part of the complex machinery of evolution, the genetics is programmed ultimately to end life. At a certain age the body down regulates factors that cause the human body to decline ​and ultimately dieIt is also believed ​that their is a hard genetic cut off switch ending life. Centenarians run in families (genetic cause) and some say that the genetics of the mitochondria in centenarians differs from that of a short-lived person. Progeria is an extremely rare autosomal dominant genetic disorder in which symptoms resembling aspects of aging are manifested at a very early age. Progeria is one of several progeroid syndromes. Those born with progeria typically live to their mid-teens to early twenties. Progeria is caused by mutations that weaken the structure of the cell nucleus, making normal cell division difficult. The histone mark H4K20me3 is involved in Hutchinson-Gilford Progeria syndrome caused by de novo mutations that occurs in a gene that encodes lamin A. Lamin A is made but is not processed properly. This poor processing creates an abnormal nuclear morphology and disorganized heterochromatin. ​Patients also do not have appropriate ​DNA repair, and they also have increased genomic instability. Genetics is so complex that the result is hundreds if not thousands of years of well intended snake oils and years wasted on therapies of limited or inadequate success, possibly a complex situation where a result is impossible and unobtainable. Progeria is a key insight in both genetic errors and cell deformation causing health problems, suggesting that both theories of aging may be correct. Is a hormone or protein later in age produced in correct quantity but perhaps cannot exit the subtle deformity of an aged cell? The difference between a nutrient entering the cell or not is so small that perhaps the aged cell struggles to accept nutrients through its slightly deformed pores and so on. Inbreeding expressing defects in the genome that present as pathology in the body, the likelihood of health issues and early death is increased. Birth defects and DNA damage cell damage relating to nuclear radiation. See how visually the shape of nucleus tells of a problem, that is to consider in cell biology, the slender shapes, the good formations, ​we are talking about micron ​deformation here. The cell has to be perfect. These are pathologies that look like aging. When doctors talk of fatty acid build up or some other situation what they are really saying is your cells are aging, and they are not behaving like the cells of a young person due to aging. ​While eating chopped up garlic may clear fatty acids build up, the cell dysfunction is a much larger problem that continues unaddressed and their medications do not address this understanding. To compare the cells of a young person who has no pathology with the cells of an old person is of a lower performance in every measure. Fatty acid build up, leaky blood brain barrier, hearing, sight and so on every comparison in every way says that the old person is not performing as well as the young person. ​While the insight ​is useful at identifying key declinesreducing medicating for cholesterol does not address ​the higher cause of cell biology of age. +The difference being male or female is said to be the instructions within the XX chromosome or the XY chromosome. The male produces both types, when the specific gene is read the instruction is a boy or a girl. Some reptiles have an environmental determinate,​ for example hot outside, a male versus cold outside, a female. This illustrates epigenetics and the powerful machine of genetics. One theory of aging is that as part of the complex machinery of evolution, the genetics is programmed ultimately to end life. At a certain age the body down regulates factors that exposes ​the human body to decline ​leading to deathThere is also some very scant evidence ​that even if aging were to be stopped and every cell in your body was perfect that death would still occur. Centenarians run in families (genetic cause) and some say that the genetics of the mitochondria in centenarians ​(which come via the ovum, the mother) ​differs from that of a short-lived person. Progeria is an extremely rare autosomal dominant genetic disorder in which symptoms resembling aspects of aging are manifested at a very early age. Progeria is one of several progeroid syndromes. Those born with progeria typically live to their mid-teens to early twenties. Progeria is caused by mutations that weaken the structure of the cell nucleus, making normal cell division difficult. The histone mark H4K20me3 is involved in Hutchinson-Gilford Progeria syndrome caused by de novo mutations that occurs in a gene that encodes lamin A. Lamin A is made but is not processed properly. This poor processing creates an abnormal nuclear morphology and disorganized heterochromatin. DNA effects cell morphology which in turn effects DNA processing. The pituitary gland begins to lag in performance in part due to deformlumpy and shrunken with age. Genetics is so complex that the result is hundreds if not thousands of years of well intended snake oils and years wasted on therapies of limited or inadequate success, possibly a complex situation where a result is impossible and unobtainable. Progeria is a key insight in both genetic errors and cell deformation causing health problems. Inbreeding expressing defects in the genome that present as pathology in the body, the likelihood of health issues and early death is increased. Birth defects and DNA damagecell damage relating to nuclear radiation. See how visually the shape of nucleus tells of a problem, that is to consider in cell biology, the slender shapes, the good formations, ​these are micron ​deformations. The cell has to be perfect. These are pathologies that look like aging. When doctors talk of fatty acid build up or some other situation what they are really saying is your cells are aging, and they are not behaving like the cells of a young person due to aging. ​It is said the cell loses its identity and begin to behave like a fat cell which is what the fatty build up is. The cell dysfunction is a much larger problem that continues unaddressed and their medications do not address this understanding. To compare the cells of a young person who has no pathology with the cells of an old person is of a lower performance in every measure. Fatty acid build up, leaky blood brain barrier, hearing, sight and so onevery comparison in every way says that the old person is not performing as well as the young person. ​Cell biology ​is the start of new medicine. If they cannot cure progeriathey will not be able to cure aging, if they can not turn on and turn off puberty at the genetic level, they will not be able to cure aging, if they cannot regenerate tooth in old age, then they will not be able to cure agingSuch is the reality check. Articles: [[removing_wrinkles_inside_our_cells_might_reverse_aging|1]],​ [[neuroscientists_discover_anti_aging_molecule_repairs_age_related_dna_damage|2]]
  
 The Horvath age estimation algorithm (2013), found 353 epigenetic bio markers of human aging, according to which the chronological age of a person was determined with an accuracy of 1.5 years, death date can be predicted to an accuracy of 1.5 years and these bio markers can change depending on epigenetic behaviours like fasting or exercising so a practice can be investigated to be beneficial or not by its effect on the bio markers. The Horvath age estimation algorithm predicts DNAm age based on the methylation levels of 353 CpGs. DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation typically acts to repress gene transcription. In mammals, DNA methylation is essential for normal development and is associated with a number of key processes including genomic imprinting, X-chromosome inactivation,​ repression of transposable elements, aging, and carcinogenesis. Correlation or causation? In a study at Kings College London using groups of identical twins, researchers found 490 age related epigenetic changes that could be used as a guide to the stages of biological ageing. Their are other biomarker systems to test efficacy of proposed experimental treatment. The Horvath age estimation algorithm (2013), found 353 epigenetic bio markers of human aging, according to which the chronological age of a person was determined with an accuracy of 1.5 years, death date can be predicted to an accuracy of 1.5 years and these bio markers can change depending on epigenetic behaviours like fasting or exercising so a practice can be investigated to be beneficial or not by its effect on the bio markers. The Horvath age estimation algorithm predicts DNAm age based on the methylation levels of 353 CpGs. DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation typically acts to repress gene transcription. In mammals, DNA methylation is essential for normal development and is associated with a number of key processes including genomic imprinting, X-chromosome inactivation,​ repression of transposable elements, aging, and carcinogenesis. Correlation or causation? In a study at Kings College London using groups of identical twins, researchers found 490 age related epigenetic changes that could be used as a guide to the stages of biological ageing. Their are other biomarker systems to test efficacy of proposed experimental treatment.
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 Hormone therapy, aging people should probably be on some type of hormone therapy or doing excercises to promote hormone production. Hormones are the first way to make a person feel as though they are not aging. Hormones will effect stength and energy levels, libido and mood. The problem with hormone therapy is their is no easy way to add hormones, the dystophy to the endochrine system such as the testicles and that can lead to over a year of no production of hormones after the treatment is stopped and understanding safe levels, the health effect of a hormone and if a hormone does what we believe it does. Hormone therapy, aging people should probably be on some type of hormone therapy or doing excercises to promote hormone production. Hormones are the first way to make a person feel as though they are not aging. Hormones will effect stength and energy levels, libido and mood. The problem with hormone therapy is their is no easy way to add hormones, the dystophy to the endochrine system such as the testicles and that can lead to over a year of no production of hormones after the treatment is stopped and understanding safe levels, the health effect of a hormone and if a hormone does what we believe it does.
  
-Although when we discuss aging, we are only really referring to one experiment and that experiment is parabiosis. Parabiosis is surgically connecting a young mouse to an old mouse so that they share a common blood stream. It is said that the old mice rejuvenates due to young blood. In the mid-1800s, parabiotic experiments were pioneered by Paul Bert. He postulated that surgically connected animals could share a circulatory system. Bert was awarded the Prize of Experimental Physiology of the French Academy of Science in 1866 for his discoveries.+Although when we discuss aging, we are only really referring to one experiment and that experiment is parabiosis. Parabiosis is surgically connecting a young mouse to an old mouse so that they share a common blood stream. It is said the old mouse rejuvenates due to young blood. In the mid-1800s, parabiotic experiments were pioneered by Paul Bert. He postulated that surgically connected animals could share a circulatory system.
  
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 The old mouse gets younger but the young mouse gets older. The old mouse gets younger but the young mouse gets older.
  
-The gold standard ​is this discussion ​is the blood of a young athletic person, ​we know that umbilical cord blood Wharton jelly is superior ​but relates to stem cells which is a regenerative treatment ​part of the bodies regenerative systemwhile this section ​concerning supplementation ​degradation issues with age. The reference or comparison is the biological difference between the blood of a young athlete and every one else and such can be measured. The theory is, young people have levels of proteins that are rejuvenating and old people have levels of proteins that promote aging, at a certain cell age, age promoting secretions increase. The treatment is to add more of a specific protein and subtract an over amount of a specific protein and simply ​synchronize the old blood to look like the young blood in the different levels of proteins or [[blood_composition|blood composition]]. In practice, it matters less as to why young blood improves health span, but rather the safe dosages of specific factors relative to a recipient. If safe levels could be formulated then research could potentially advance more quickly in terms of finance and availability,​ willingness of human test subjects. In a study contrasting a young person and an old person, degradation is in every place in the body and asking why improves the treatment. It is not enough to add young blood instead also the removal of old blood, one I.V taking old blood out and another I.V putting young blood in, adding ​plasma ​is not enough ​the high level of aging proteins must be taken out. The blood temperature must remain at 37° Celsius at all times as heating the blood and perhaps cooling the blood ruins the rejuvenating factors. Male blood must go to males, and female blood must go to females because of differing hormone levels and pre and post menopausal considerations. The issues with a whole blood transfusion is someone will screw up blood types, minor issue of pathogens or adverse reactions, DNA differences,​ or a blood trafficking black market where a bag of blood is stolen and resold in "freedom" town for $8,000. Air contamination into the blood stream and TACO Transfusion associated circuitry overload, as extraction and infusion are both required keeping blood levels adequte and consistant through the transfusion might require computerized biomedical machine, as we are not just dumping blood in, vital signs can be monitored and biomedical machine alterates accordingly. Transfusion studies show 1% of people die during transfusions so precautions must be taken to eliminate TACO. Their may be as much as 20,000 proteins in blood so whole blood is the best you can get while further on it may be about putting the old blood into a biomedical [[blood_filtration_system|blood processing machine]] that takes aging proteins out and adds young proteins in and then pumps it back into the body (stroke could be triggered, should air get into the bloodstream). It is unlikely to be a pill that neutralizes aging factors and tops up young factors but instead requires blood processing. It is not a single protein, those geared towards sugar pills wished it was a single protein, and they have put resources into isolating a single protein but that possibility is gone while it is still a relatively simple matter of synchronizing the composition of the aged blood to the young blood we are well into the pharmaceutical game of drug creation, one protein cannot make it rain so one protein might still treat or benefit one pathology and its source ​is blood factors. They are only interested in pills what is ignored is what cannot be put into a bottle, the reality is the human body is far more complex, their are 2 to 3 thousand G protein-coupled receptors (GPCR'​s constitute a large protein family of receptors that detect molecules outside the cell and activate internal signal transduction pathways and, ultimately, cellular responses, see ligands & receptors) in each cell accessing, switching genes constantly. Pre-clinical health span will require infusions not pills (and possibly computers monitoring and deciding). The companies who get their infusion expertise correct and first class will rule the regenerative medicine scene. One concern with infusions is fads, do not infuse metformin or resveratrol, young people's blood does not so these are foreign to the body and do not put us on the path towards cell biology. Another concern is more is better, super doses are not better. ​You must be alert to company, business money making objectives and their bad advice rather than the reality which is young people do not need medications so ultimately the therapy should yield the same result. The question is, does the body of a young person ​makes that factor, if not then it should not be there regardless of the science, if the body does not produce that factor do not infuse that factor! If the body has a certain mg of that factor do not exceed that dosage. Their are interrelationships where overdosing causing adverse effects in associated systems. ​ +The gold standard is the blood of a young athletic person, umbilical cord bloodWharton jelly is well established ​but relates to stem cells which is a regenerative treatment, this section ​concerns supplement ​degradation issues with age. The reference or comparison is the biological difference between the blood of a young athlete and every one else and can be measured. The theory is, young people have levels of proteins that are rejuvenating and old people have levels of proteins that promote aging, at a certain cell age, age promoting secretions increase. The treatment is to add more of a specific protein and subtract an over amount of a specific protein and synchronize the old blood to look like the young blood in the different levels of proteins or [[blood_composition|blood composition]]. In practice, it matters less as to why young blood improves health span, but rather the safe dosages of specific factors relative to a recipient. If safe levels could be formulated then research could potentially advance more quickly in terms of finance and availability,​ willingness of human test subjects. In a study contrasting a young person and an old person, degradation is in every place in the body and asking ​"why?" ​improves the treatment. It is not enough to add young blood instead also the removal of old blood, one I.V taking old blood out and another I.V putting young blood in, adding ​blood is not enoughproteins ​that promote aging must be taken out. The blood temperature must remain at 37° Celsius at all times as heating the blood and perhaps cooling the blood ruins the rejuvenating factors. Male blood must go to males, and female blood must go to females because of differing hormone levels and pre and post menopausal considerations. The issues with a whole blood transfusion is someone will screw up blood types, minor issue of pathogens or adverse reactions, DNA differences,​ or a blood trafficking black market where a bag of blood is stolen and resold in "freedoms" town for $8,000. Air contamination into the blood stream and TACOTransfusion associated circuitry overload, as extraction and infusion are both required keeping blood levels adequte and consistant through the transfusion might require computerized biomedical machine, as we are not just dumping blood in, vital signs can be monitored and biomedical machine alterates accordingly. Transfusion studies show 1% of people die during transfusions so precautions must be taken to eliminate TACO. Their may be as much as 20,000 proteins in blood so whole blood is the best you can get while further on it may be about putting the old blood into a biomedical [[blood_filtration_system|blood processing machine]] that takes aging proteins out and adds young proteins in and then pumps it back into the body (stroke could be triggered, should air get into the bloodstream). It is unlikely to be a pill that neutralizes aging factors and tops up young factors but instead requires blood processing. It is not a single protein, those pill pushers ​geared towards sugar pills wished it was a single protein, and they have put resources into isolating a single protein but that possibility is gone while it is still a relatively simple matter of synchronizing the composition of the aged blood to the young blood we are well into the pharmaceutical game of drug creation, one protein cannot make it rain so one protein might still treat or benefit one pathology and the gift the keeps on giving ​is blood factors. They are only interested in pills what is ignored is what cannot be put into a bottle, the reality is the human body is far more complex, their are 2 to 3 thousand G protein-coupled receptors (GPCR'​s constitute a large protein family of receptors that detect molecules outside the cell and activate internal signal transduction pathways and, ultimately, cellular responses, see ligands & receptors) in each cell accessing, switching genes constantly. So what we send into the blood speaks to the genitics. Pre-clinical health span will require infusions not pills (and possibly computers monitoring and deciding). The companies who get their infusion expertise correct and first class will rule the regenerative medicine scene. One concern with infusions is fads, do not infuse metformin or resveratrol. Young healthy ​people ​do not take medication and so the goal is the treatment should ​not either. Another concern is more is better, super doses are not better. ​Young people do not need medications so ultimately the therapy should yield the same result. The question is, does the body of a young person ​make that factor, if not then how are we heading in the right direction by adding foreign chemicals? It should not be there regardless of the science, if the body does not produce that factor do not infuse that factor! If the body has a certain mg of that factor do not exceed that dosage. Their are interrelationships where overdosing causing adverse effects in associated systems. ​Howeverconvalescent plasma treatment ​and blood transfusions are well tolerated and widely used.
-Comparing fluid composition and synchronizing identical to a young person at safe dose is not cell biologyit does not answer all the question ​and it does not supposed to, but it may instead if delivered intelligently keep you pre-clinical for longer.+
  
-To help you understand... the two biggest performance enhancing drugs on Earth are testosterone ​and human growth hormoneboth are called anabolic steroids ​and both are produced by the human body and secreted into the blood, humans learned of both these from the human body not plants. With aging the body produces less of these hormones resulting in decline. This is not like some vitamin pill or omega 3 pills, if you receive these two hormones intravenously (I.V) or injection you will feel the difference, quality of life. Take collagen, produced naturally by the body decreases with age, supplementation with collagen to young level might have a myriad of pre-clinical ​health benefits+Comparing fluid composition ​and synchronizing identical to a young person at safe dose is not cell biologyit does not answer all questions ​and it does not suppose tobut it may instead ​if delivered intelligently keep pre-clinical ​for longer.
  
-The richest source of young blood is Umbilical cord blood or Whartons jelly+To help understand... the two biggest performance enhancing drugs on Earth are testosterone and human growth hormone, both are called anabolic steroids and both are produced by the human body and secreted into the blood, humans learned of both these from the human body not plants. With aging the body produces less of these hormones resulting in decline. This is not like some vitamin pill or omega 3 pills, if you receive these two hormones intravenously (I.V) or injection you will feel the difference. Take collagen, produced naturally by the body decreases with age, supplementation with collagen to young level might have a myriad of pre-clinical health benefits 
  
 A recent study, [[https://​ganino.com/​files/​2020.05.07.082917v1.full.pdf|Reversing age: dual species measurement of epigenetic age with a single clock]], the results are significant enough to prompt further interest. A recent study, [[https://​ganino.com/​files/​2020.05.07.082917v1.full.pdf|Reversing age: dual species measurement of epigenetic age with a single clock]], the results are significant enough to prompt further interest.
  
-You cannot eat turmeric to ameliorate the inflammation response. Understanding inflammation. When a person cuts themselves or bumps their head the area becomes inflammed or swelling, inflammation is initial response to tissue damage. ​The human body has its own system for treating inflammation and either naturally or by infusion, activation ​of the system to ameliorate inflammation ​is the only correct means to treat the inflammation. After which the body activates its regenerative,​ healing, repair system to heal the area. Not turmeric, grape juice, ​or another substance. Inflammation increases with aging and this may be due to the difference in cell morphology and the body sees an aged cell as damaged and thus the inflammatory reponse. The remedy of which is the innate regenerative response, which is severely limited with age. Activation and empowering the regerenative system is an ongoing study with many applications.+The richest source ​of young blood is Umbilical cord blood or Whartons jelly.
  
-We always hear about the immune system but the body also has a regenerative system, when a person cuts themselves it heals. Focusing in on this system and making it more capable and more powerful. ​Their is also stem cell therapies where either pluripotent young cells are injected into person, and they lend their factors (growth factors) to the body causing healing or rejuvenation. Such as mesenchymal stem cells. The cells do not have matching DNA, so they are rejected by the immune system but their is an attempt to have them lend their growth factors to existing cells to have them heal faster and run better before the immune system eats them, this therapy might be more effective if the MSC were edited to have matching DNA and matching mitochondria DNA with the patient. This field of stem cells has an very evil temptation and that is using aborted babies as the ideal stem cells for therapies. In some places abortion laws have been quietly altered to facilitate the harvesting of aborted babies. These are not Embryonic Stem Cells nor are they Umbilical cord cells or blood instead Fetal Stem cells, the remains of aborted babies and their are some ugly people that want to absorb them. However, fetal remains are not particularly necessary as their are several other ways to obtain stem cells. Stem cell technology is not ready yet. [[https://​www.thefreelibrary.com/​Do+liver+stem+cells+come+from+bone+marrow%3f-a063692734|Do liver stem cells come from bone marrow]]+{{ ::​stem-cell-aging-.jpg?​direct&​500|Show how available replacement cells dimish with age, causing reduced healing}} 
 + 
 +You cannot eat turmeric to ameliorate the inflammation response. Understanding inflammation. When a person cuts themselves or bumps their head the area becomes inflamed or swells, inflammation is initial response to tissue damage. The human body has its own system for treating inflammation and either naturally or by infusion, activation of the system to ameliorate inflammation is the only correct means to treat the inflammation. After which the body activates its regenerative,​ healing, repair system to heal the area. Not turmeric, grape juice, or another substance. Inflammation increases with aging and this may be due to the difference in cell morphology and the body sees an aged cell as damaged and thus the inflammatory response. The remedy of which is the innate regenerative response, which is severely limited with age. Activation and empowering the regenerative system is an ongoing study with many applications. 
 + 
 +We always hear about the immune system but the body also has a regenerative system, when a person cuts themselves it heals. Focusing in on this system and making it more capable and more powerful. ​There are also stem cell therapies where either pluripotent young cells are injected into person, and they lend their factors (growth factors) to the body causing healing or rejuvenation. Such as mesenchymal stem cells. The cells do not have matching DNA, so they are rejected by the immune system but the attempt to have them lend their growth factors to existing cells to have them heal faster and run better before the immune system eats them, this therapy might be more effective if the MSC were edited to have matching DNA and matching mitochondria DNA with the patient. This field of stem cells has very evil temptation and that is using aborted babies as the ideal stem cells for therapy. In some places abortion laws have been quietly altered to facilitate the harvesting of aborted babies. These are not Embryonic Stem Cells nor are they Umbilical cord cells or blood instead Fetal Stem cells, the remains of aborted babies and there are some ugly people that want to absorb them. However, ​it is not understood how fetal remains are applicable ​to our use of if they have any use. [[https://​www.thefreelibrary.com/​Do+liver+stem+cells+come+from+bone+marrow%3f-a063692734|Do liver stem cells come from bone marrow]] 
 + 
 +Exosomes or mesenchymal stem cells or both? Exosomes from healthy cells carry much of the regenerative proteins of the Mesenchymal Stem Cell and the Exosomes fit the definition of Nan Particles. As Nano particles Exosomes are very small and can penetrate the Blood Brain Barrier. It is believed that much or all of the positive outcomes believed to have been attributed to Mesenchymal Stem Cells for the treatment of neurodegenerative disorders are due to the Exosomes from the Mesenchymal Stem Cells. Many scientists now believe that you are skipping right to the Regeneration process by using Exosomes as opposed to Mesenchymal Stem Cell’s while avoiding, or at the very least, mitigating the risk of rejection and problems associated with inflammation. Both exosomes and MSC's can come from various places in the body plus placenta, umbilical cord. 
 + 
 +Exosomes have messenger RNA, micro RNA and proteins and made by cell and transfer these contents to other cells. There might be a way to make a transgenic cow that produces human exosome in the milk as they are nan particles, they are bio-available and the milk simply consumed. 
 + 
 +There are several places where you can receive an injection of mesenchymal stem cells or exosomes, some people claim great success others not. I do not believe that bone marrow or adipose stem cells are effective in comparison to Wharton jelly. The therapy is required either every year or every three years and constitutes one I.V session lasting several hours, with effects either instantly and progressing over several months. Expertise is crucial here, the most established practitioners are possibly the Riordan clinic in Panama (MSC'​s),​ and Prmedica exosome clinic in Mexico.
  
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 The mice that drank the most quickly died. But the mice that drank a limited dose did not develop tumors. Instead, they became more physically robust, their kidneys and spleens worked better, and their hearts pumped harder. In all, the treated mice lived 30% longer than their littermates. The mice that drank the most quickly died. But the mice that drank a limited dose did not develop tumors. Instead, they became more physically robust, their kidneys and spleens worked better, and their hearts pumped harder. In all, the treated mice lived 30% longer than their littermates.
  
-A Stanford team described a feasible way to deliver Yamanaka factors to cells taken from patients, by dosing cells kept in cultures with small amounts of the factors. If dosed for a short enough time, the team reported, the cells retained their identity but returned to a youthful state, as judged by several measures of cell vigor. A Stanford team extracted aged cartilage cells from patients with osteoarthritis and found that after a low dosage of Yamanaka factors the cells no longer secreted the inflammatory factors that provoke the disease. The team also found that human muscle stem cells, which are impaired in a muscle-wasting disease, could be restored to youth. Members of the Stanford team have formed a company, Turn Biotechnologies,​ to develop therapies for osteoarthritis and other diseases. Another company is AgeX and GenuCure developing various treatments heart tissues, osteoarthritis,​ aging-related muscle loss, rejuvenating cartilage.+A Stanford team described a feasible way to deliver Yamanaka factors to cells taken from patients, by dosing cells kept in cultures with small amounts of the factors. If dosed for a short enough time, the team reported, the cells retained their identity but returned to a youthful state, as judged by several measures of cell vigor. A Stanford team extracted aged cartilage cells from patients with osteoarthritis and found that after a low dosage of Yamanaka factors the cells no longer secreted the inflammatory factors that provoke the disease. The team also found that human muscle stem cells, which are impaired in a muscle-wasting disease, could be restored to youth. Members of the Stanford team have formed a company, Turn Biotechnologies,​ to develop therapies for osteoarthritis and other diseases. Another company is AgeX and GenuCure developing various treatments heart tissues, osteoarthritis,​ aging-related muscle loss, rejuvenating cartilage. ​[[old_human_cells_rejuvenated_stem_cell_technology|1]]
  
-Other scientists are experimenting with the factors, by leaving some out or another derivative cell quality improves and cancer is less probable. ​ +Other scientists are experimenting with the factors, by leaving some out or another derivative cell quality improves and cancer is less probable ​while others are including more factors than the four, OSKM. The major problem is seperating aging from ipsc, they are struggling to get significant age reveral before going too far, high dose and reverting the cell to ipsc. They are using RNA's which degrade quickly, have no permanent effect and have the possibility to be systemic perhaps in a vesicle. It matters less as to effectiveness at this stage rather that any therapy even modest is safe. The situation might require a reprogramming blocker, after an RNA partially reprogrames,​ another RNA makes the cell immune to further re-programming allowing systemic uniform partial reporgramming. The RNA will eventually dissolve and the cell becomes partially reprogrammable again.
  
-===== Cell Replacement ​Autophagy ​Therapy =====+===== Cell Replacement Therapy ​In Situ =====
  
-Humans are made up of very elaborate mechanisms ​and machinesThese mechanisms ​and machines ​need to function correctly and optimally all the time for a person to be "​healthy"​. It is said that every day 50 to 70 billion cells die (are signalled to self destruct) and are replaced ​out of an estimated total 30 to 40 trillion cells no one knows for sure in the human body. Humans have no way to grade the cells in the human body to see if they are functioning completely correctly, if they are functioning at an optimal level. Attempting to save your cells is probably a lost cause instead optimal replacement. There might be ways to add optimal, functional and young or athletic ​cells to the human body [[https://​www.sciencedaily.com/​releases/​2020/​03/​200330093410.htm|without rejection]]. Would simply replacing and upgrading cells on an ongoing basis be enough to guarantee health span and maximum lifespan? Would it add insight into damage theory vs genetic theory of aging? We may never know. Cell replication is called mitosis, ​and some cells can divide (skin cells) and use a neighbouring skin cell to replace a cell while other cells lose their ability to replicate (liver cells) and require the bodies ​store of stem cells (bone marrow) to arrive at site to replicate ​and differentiate.+The body is 100% made of cells, cell morphology including genetics, epigenetics are the source ​and cause of many pathologies so cell quality is importantCells degrade and get damaged and most are replaced, with age even replacement cells come defective from the beginning. Human beings have an estimated 30 to 40 trillion cells in total, no one knows for sure in the human body. Cells are highly complex ​and need to function correctly and optimally all the time for a person to be "​healthy"​. It is estimated ​that each day 50 to 70 billion cells die (signalled to self-destruct, apoptoses) and are replaced ​as part of body's natural processThey are either replaced by an adjoining cell or by stem cells located at their nearby pericyte, produced by the bone marrow. Cell replication is called mitosis, some cells can divide (skin cells) and use a neighbouring skin cell to replace a cellother cells partially ​lose their ability to replicate (liver cells) ​while and require the body'​s ​store of stem cells (bone marrow) to arrive at site to repair, while other cells lose their ability to repair such as brain nurons ​and are not replaced. Various people argue for saving the cell as if the exact same cells exist in the body for ones entire life, in fact the body replaces cells ongoing to maintain optimal body.
  
-Their was a time it was believed ​that genetic engineering was biology'​s holy grail instead today we have to consider the entire cell not just the DNACell biology includes genetic engineeringThe crossroad of health span and lifespan is the cell, if we master the cell we master all pathologiesThe gold standard cell is the young cell and any deviation is troublingthe reasons of illness ​are that the cell is behaving incorrectlyThe cell or the protein it manufactures may be malformed ​in some way or produced or released in low numberSickle cell diseaseprogeriacancer and many more are cell dysfunction pathologies where for example the DNA stop sequence has malfunctionedHow are you going to verifydetect and remedy such occurrences?​ Can you say cell number ​trillion does not have the stop sequence or potassium delivery in cell number 2 trillion is sub-optimal? Their seems to be nucleus deformation ​on cell 1 billion? Sub-optimal ATP production in mitochondria cell number 7 trillion. That would be the right procedure to perform.+Some organs are highly regenerative while some not, it is often stated ​that on average, cells in a human body are replaced every 7 to 10 yearsRed blood cells 4 months, white blood cells over 1 yearSkin cells: 2 or 3 weeks. Colon cells: ~4 daysBrain cells typically last an entire lifetime (neurons in the cerebral cortex, for example, are not replaced when they die)Neutrophil cells (a type of white blood cell) might only last 2 days, while the cells in the middle of your eye lenses will last your entire lifeBrain cells: 200+ years? Eye lens cells: LifetimeHeart muscle cells: 40 yearsIntestinal cells (excluding lining): 15.9 yearsSkeletal muscle cells: 15.years, Fat cells: 8 years, Haematopoietic stem cells: 5 years, liver cells: 10-16 months, Pancreas cells: 1 year and so on.
  
-therapy might be to manufacture higher quality cells outside the body and then introduce them into the body (ex in vitro). ​The procedure would be to take stem cells from a young sourcecell is graded for its slender curves and superior specimen it was derived from. They must be pluripotentThe DNA code from the patient ​cell is uploaded ​to the new cell possibly using the CAS 9 protein or another meanscareful not to deform ​the gradients ​with instrumentsBoth the mitochondria DNA and the cell DNA both are identical to the recipient, the DNA material ​is optimal ​and the code error checked among many cells. ​Culture them and grade them and possibly add visual marker ​to the cell. Using an aggressive synoletic or pre-synoletic perhaps one that detect short telomeres ​ or another ​cell age marker ​and send it the signal ​to apoptose or the use of a sonic scalpel destroy a certain amount of for example liver cells in the patient (who has the liver problem) and doing so will activate the body to produce and send its own bone marrow stem cells to the site for repair ​instead you want to inject the patient with the lab derived ​stem cells (along with MSC'​s) ​with the intent that the body utilizes ​them instead for repair. The procedure would mean that the cells at the liver are of a higher grade than those from the bone marrow and thus more healthy. Repeat the procedure until the liver is replaced. ​This treatment ​is required every day so that all the cells in the human body are eventually comprised of the lab grown superior cellThe aged person ​will not be able to keep up with the repair regiment and so need custom cells ready made infused. The theory ​is if the cells are kept young the person lives forever but suspect that their is a genetic hard switch.+When 50 to 70 billion cells die each day and are replaced, how do we get better cells to take their place? Not only the 50 to 70 billion cells each day but also in the regeneration and maintenance of organs in situ. Unless we can up regulate the condition of these replacement cells, aging will occur. 
 + 
 +There are those that want to focus on the source of these replacement cells with a targeted therapy to keep them young, bone marrow age reversal treatments so the stem cells produced are of better quality such as pharmaceutical target CDC42, as the cause of stem cell aging. 
 + 
 +Grading cells to see if they are functioning completely correctly at an optimal level is not a therapy. The pharmaceutical cell removal agents called synolytics are also of questionable effectiveness. The immune system plays the major role of daily disposal of damaged cells, there is autophagy after fasting, but we do not manually verify, detect and remedy damaged cells. Can we say cell number 1 trillion does not have the stop sequence or potassium delivery in cell number 2 trillion is sub-optimal?​ There seems to be nucleus deformation on cell 1 billion? Sub-optimal ATP production in mitochondria cell number 7 trillion and so on. Tag those and remove, that would be the right procedure to perform. There is no M.R.I like machine that can perform this task on a cell by cell basis. 
 + 
 +Taking advantage of the cell renewal process, the obvious ​therapy might be to manufacture ​the higher quality cells outside the body and then introduce them into the body (ex in vitro) ​along with the various additional proteins the body dispatches when there is a woundThese cells are younger than existing cells in the body and with sophisticated treatment the body is kept from aging by providing ​young cellspractically biologically new. 
 + 
 +The reason we have not seen large scale stem cell treatments ​is immune system rejection, just like in organ transplants. The field is called "stem cell immunobiology"​. They have saying for over 10 years that stem cells have the potential to create organs without immune rejectionThat is not the case. 
 + 
 +Groups seek to produce off the shelf stem cell product that is not rejected by the immune system. To quote Dr. Sonja Schrepfer "Our team used CRISPR ​to create ​the first pluripotent stem cells that are functionally '​invisible'​ to the immune systema feat of biological engineering that prevents rejection of stem cell transplants and brings the promise of regenerative medicine a step closer ​to becoming reality"​ and "In our paper, we describe how, by altering ​the activity of just three genes in pluripotent stem cells, these triple-engineered stem cells are able to avoid rejection after being transplanted into histocompatibility-mismatched recipients ​with fully functional immune systems." [[https://​www.nature.com/​articles/​s41587-019-0016-3|Hypo immunogenic derivatives of induced pluripotent stem cells evade immune rejection in fully immunocompetent allogeneic recipients]]. The first time I heard of this was by Claudia Mitchell, Ph.D., CEO Seattle, WA of Universal Cells ini 2017. 
 + 
 +[[https://​www.businesswire.com/​news/​home/​20200529005130/​en/​AgeX-Therapeutics-Sernova-Collaborate-Engineer-Universal-Locally|AgeX Therapeutics and Sernova to Collaborate to Engineer Universal Locally Immune Protected Cell Therapies for Type I Diabetes and Hemophilia A]], its trial use in humans dated June 2020.  
 + 
 +If what she states is correct, it will be possible to have modest cell replacement therapies. These cells offer regenerative medicine and it is all that we want. But... in my opinion, ​the immune system cloak of knocking the three genes is a problem. The function of these three genes is so the immune system can detect ​and destroy ​the cell because it is malfunctioning and without this monitoring of the cellwhen these universal cells become dysfunctional ​the immune system ​is blind to their state. If a virus gets into one of these cells it will replicate indefinitely ​and the immune system will be blind to where it is coming from and the person will die. These problems need to be solved otherwise the cells will not be fit for useIts solution might be in finding biomarkers of cell dysfunction ​and attaching those markers to apoptoses using genetic engineering,​ or there might be other ways for universal stem cells to pass the immune system check without gene editing ​and that would be better case. What if the cells are generated in the body, does the familiar environment provide some critical identification factor making them pass the immune system? Due to these unknowns ​the universal stem cell is sub-standard to a healthy human, but a step up for a sick person. 
 + 
 +This has the potential to make humans partially transgenic. One of these cells take up residence with the human body, that body is regarded as transgenic. Transgenic means [[genetic engineering]]. These cells can be genetically engineered to do any actions as much as intelligence can instil in cell. The stem cell is a programming platform, hopefully an open source platform. Once that cell is expanded the genetic program is in every cell. This may begin with a modest 0.001% transgenic human and increase with popularity of the therapy with an eventual maximum possible transgenic percentage. A transgenic embryo would be 100% transgenic person, genetically engineered, infusing cell will never make a 100% transgenic human. 
 + 
 +Such a therapy for universal stem cells, each month a person would come in and be infused with a bag of universal stem cells, as the body is replacing cells all the time the infused cells are incorporated. These stem cells are younger than the body's cells and also have special abilities that have been genetically coded into them. Or if a person has an issue with an organ that requires organ transplant, intentional wounds are made to the organ in order to remove as many diseased cells in a session, this can be done using a sonic scalpel ​called [[science:​sound_weapons|histotripsy]] can destroy a certain amount of for example liver cells in the patient (who has the liver problem). This is will cause the body to attempt to repair the wound, ​and will activate the body to produce and send its own bone marrow stem cells to the site for repair. At the same time inject the patient with universal ​stem cells (along with the identical mixture the such MSC'​s) ​and hope the body utilizes the lab grown cells instead ​of the body's cells for the repair. Repeat the procedure until the liver is replaced. 
 + 
 +It is a simple idea, the ongoing continual renewal of cells from young universal stem cells is predicted to have a major effect on agingNo person ​is able to get younger cells replacing their current cells, due to the immune system ​so it is uncertain what effect it would have. If the crucial to aging organs and cells were biologically new and kept biologically new in an aging body, perhaps it will lead to the discovery of organs relating to longer lifespan. 
 + 
 +[[https://​www.nature.com/​articles/​s41467-020-16455-7|Improving the safety of human pluripotent stem cell therapies using genome-edited orthogonal safeguards]] \\ 
 +[[https://​www.sciencedaily.com/​releases/​2020/​03/​200330093410.htm|Advances in production of retinal cells for treating blindness]] \\ 
 +[[https://​www.ncbi.nlm.nih.gov/​pmc/​articles/​PMC6332789/​|Direct in vivo application of induced pluripotent stem cells is feasible and can be safe]] \\ 
 +[[https://​www.medindia.net/​news/​healthinfocus/​why-does-your-body-reject-your-own-stem-cells-189730-1.htm|Why Does Your Body Reject Your Own Stem Cells?]] \\ 
 +<​html><​href="​https://​www.ganino.com/​mov/​Transplants without Immunosuppressant Drugs UCSFs Transplant and Stem Cell Immunobiology Lab.mp3">​Transplants without Immunosuppressant Drugs UCSFs Transplant and Stem Cell Immunobiology Lab</​a></​html> ​ Finding Genius Podcast with Dr. Schrepfer and  Dr. Deuse.
  
 ===== Yamanaka Factor Therapy ===== ===== Yamanaka Factor Therapy =====
  
-This procedure utilizes the Yamanaka factors as a theoretical therapy. ​The two most important tools in genetic ​engineering ​is gene manipulation ​and gene expression ​control. Gene manipulation ​is changing ​the DNA code such as with sickle disease. The procedure is change ​the gene that is an error that causes sickle ​cell disease, once the gene is changed ​the body no longer has sickle ​cell disease ​and it is finishedTheir are no medications ​to take and the fix is permanent. The faulty ​gene no longer exists anywhere ​in the human body.+This procedure utilizes the Yamanaka factors as a theoretical therapy. ​Firstly, ​in normal humans and secondly in transgenic humans. The major problem here as with genetic ​vectors ​is how do get systemic, 1 cell, 1 dose. Systemic means each cell in the body gets the same dose. With transgenic the alteration is specified in the ovum and replicated throughout the organism, allowing for uniform activation later on. As genetic engineers do not have such a level of control ​without going transgeneic,​ such reveals that effective Yamanaka factors treatment have not been used in humans, possibly other than some haphazard lysate or a transgenic human. 
 + 
 +Old people should be able to regenerate new teeth when they fall out just as young people do. Gene expression control theoretically would allow for the activation of tooth regeneration in an old person, where is it? The code to do this still exists for a persons entire life but is locked from expression. How to turn it back on? What is important is that Yamanaka factors are also still in the human genome. If we can regenerate teeth we could also partially activate Yamanaka factors. Currently, no means to control genetics easily. Partial reprogramming in vivo is not outrageous, there are some real potential medical applications discussed openly.  
 + 
 +A list of papers... 
 + 
 +[[https://​www.cell.com/​fulltext/​S0092-8674(16)31664-6|In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming]] \\ 
 +[[https://​pubmed.ncbi.nlm.nih.gov/​29353456/​|In Vivo Transient and Partial Cell Reprogramming to Pluripotency as a Therapeutic Tool for Neurodegenerative Diseases]] \\ 
 +[[https://​www.stemcellsportal.com/​article-scans/​partial-reprogramming-vivo-enhances-wound-repair-mice|Partial Reprogramming in vivo Enhances Wound Repair in Mice]] \\ 
 +[[https://​www.ncbi.nlm.nih.gov/​pmc/​articles/​PMC4607754/​|Regeneration through Reprogramming Adult Cell Identity in Vivo]] \\ 
 +[[https://​www.anti-agingfirewalls.com/​2018/​09/​02/​aging-cell-and-tissue-repair-renewal-and-regeneration-inflammation-and-the-sasp/​|AGING,​ CELL AND TISSUE REPAIR, RENEWAL AND REGENERATION,​ INFLAMMATION AND THE SASP]] 
 + 
 +[[https://​www.ncbi.nlm.nih.gov/​pmc/​articles/​PMC4699832/​|In Vivo Reprogramming for Brain and Spinal Cord Repair]] \\ 
 +[[https://​www.ncbi.nlm.nih.gov/​pmc/​articles/​PMC4111367/​|In Vivo Reprogramming of Adult Somatic Cells to Pluripotency by Overexpression of Yamanaka Factors]] \\ 
 +[[https://​www.ncbi.nlm.nih.gov/​pmc/​articles/​PMC6234007/​|In Vivo Cellular Reprogramming:​ The Next Generation]] \\ 
 +[[https://​www.nature.com/​articles/​s41467-018-05059-x|AAV vector-mediated in vivo reprogramming into pluripotency]] \\ 
 +[[https://​www.nature.com/​articles/​s41587-019-0227-7|De novo mutations in mitochondrial ​DNA of iPSCs produce immunogenic neoepitopes in mice and humans]] 
 +[[partial_cellular_reprogramming_reverse_aging|]] 
 + 
 +==== Immersed In A Pool Of Water ==== 
 + 
 +Fully body immersion in a pool of water, well a lysate with Yamanka factors ​as naked RNA. The time spent in immersion relative to dose can be generally controlled, while not an internal therapy, instead a skin therapy, external therapy. Simple, safe, easy. 
 + 
 +==== Traditional Gene Therapy In Humans ==== 
 + 
 +A safe protocol for Yamanaka factor therapy in humans. 
 + 
 +The major issue is if the dose is too much, the cell becomes an induced plulipotent stem cell, leading to cancer or death. It has been established that the right dose reverses aging markers in a linear curve that ends at age 0. How do you deliver the correct dosage into the body, some cells will overdose while others will not recieve any. If you infuse, it will concentrate around the liver or kidney ​with overdose effects. You need to control where it goes and the more control you have over cell dosage the better the treatment.  
 + 
 +  - You will need to be of an ideal weight. 
 +  - You will need a synoletic, clear the body of senescent cells prior to infusion. It is not a bright idea to reverse age markers on sanescent cells. The synoletics available today are not effective enough. Their are some immune cells that act like senolytics, perhaps they are better. 
 +  - For extra insurance and to make up for ineffective synoletic, you may need to develop a T-cell to target possible cancer cells. 
 + 
 +The only therapy that I heard about is, custom RNA using an exosome. The exosome is produced ex in vitro and then infused, it travels until it enters a cell where it releases RNA and the cell produces the Yamanaka factors. Both the RNA and exosome will eventually dissolve and a repeat infusion at some time interval. 
 + 
 +Say for example you got a cow producing your custom exosomes with factors in milk and you harvest them or whatever. The ideal case in infusion is every cell gets 1 dose with 1 infusion. The closest to that goal is the ideal practice but how do you guarantee appropriate dose? 
 + 
 +Yamanaka Factor Therapy has been tried in transgenic mice without effect of overdose but how systemic was the activation?  
 + 
 +Bring the body to uniform systemic partial preprogramming with safety, Theoretical ​procedure is, exosomes are injected into the body. These exosomes have custom RNA that code for Yamanaka factors. These will enter cells randomly, the problem ​is many exosomes entering the same cell means over production of OKSM and full reprogramming. To remedy this, we also encode the RNA to produce ​an OKSM neutralizing molecule. After a certain number of factors are produced, extra molecules are also produced, having affinity for Oct8 and binding to Oct8 thus neutralizing Yamanaka factors rendering the further cell reprogramming immune. The extra production of the neutralizing molecule means any new exosome making their way into the same cell will be disabled (ideally from making factors) not from making factors, instead neutralized from effecting the cell further. This all done in sync will allow for one treatment to be fairly uniform, systemic and safe against full reprogramming. It is assumed ​that adding a molecule to Oct4 will disable Yamanaka factors. Eventually the cell will be cleaned out and immunity cleared away and subsequent treatment can occur again. Exosomes are made by cells for intercellular communication containing RNA and proteins. 
 + 
 +Secondlylooking at the matter as probabilities and ascertaining the best protocol based on probabilities. Dosage, injection area and dispersion area. Many small doses rather than one big dose and so on. Some cell will never receive a dose, while some will receive every dose. Targeting areas or organs by place of injection. 
 + 
 +Thirdly, there are some cells that concentrate relative to cell signalling system, such as certain stem cells that concentrate around inflammation. These behaviours might localize the effect and aid in probability,​ because ​once the inflammation is dissolved ​the gene therapy will not go there twice. Inflammation might be a positive tag for the treatment. 
 + 
 +Fourthly, Liquid engineering a dispersion lysate. A lysate added to the infusion to aid in a more ideal dispersion and against multiple infection of the same cell. 
 + 
 +Fifthly, there are approximately three thousand GRPC receptors on each cell, is there one that allows for one off binding, causing ​the surrounding vectors to not be able to bind, for the purpose of single dose to a sing cell
 + 
 +There are possibly several more methods raising the bar to an acceptable level, at the very least probably experiment with a skin cream to test the saturation ​and dispersion. The challenge ​is one of expertise, optimization,​ ironing out the quirksThis therapy is not extreme or invasive but requires expertise. The path is mice, dogs, test and experiment on human skin, organs, and finally full body infusion. 
 + 
 +==== Transgenic Human Experiment ==== 
 + 
 +Once a human being has reached maturity it has trillions of cells, with respect ​to gene therapy we have lost the ability to communicate with each individual cell, we just do not have that kind of technology. Instead, if we designed the genetic program, we could tell an ovum and when the body is made from that ovum our program will be replicated in every cell after that, meaning we can then communicate with every cell in that human body. This is called "​transgenic human". 
 + 
 +The germ line edited ovum will grow into a human being and our gene therapy will be systemic, such a person able to have extra abilities, with one ability at the highest, "safe Yamanaka factor expression ​in a transgenic human experiment"​.  
 + 
 +This experiment will answer many questions and put many theories to rest. 
 + 
 +Such a person would momentarily turn on safe Yamanaka factor expression with stimuli under clinical observation. Such a person would maintain an ideal physical age in every appearance and measure, even if the person were to be of age 70, they would always look and feel like a 21-year-old. 
 + 
 +This will obviously need to be a secret experiment, to answer as many science questions as possible. Mainly, if the transgenic ​human never ages, why does the transgenic human still die? 
 + 
 +The experiment is currently possible to do, but may take ample time to perfect the genetic program for safety and success. If we can get it right we would have our ethics backwards, the transgenic human will live a normal life but never age, instead stop aging at their ideal age. An ability we would all like to have. If the person wanted to age normally they would opt not to express the factors and age normally with no further involvement. 
 + 
 +If the experiment was done well, parents would opt for this procedure for their unborn children and humans would be replaced, so we must never tell of the existence of such people. The program would include....
  
-Gene expression control is just as importantwhy can not old people regenerate new teeth when they fall out when young people do regenerate their teethGene expression control theoretically would allow for the activation of tooth regeneration in an old personThe code to do this still exists for persons entire life but is locked from expression.+  * Apoptoses () - apoptoses of senescent cells must be performed prior to OSKM activation.  
 +  * Teratomas () - safety detect and remove malfunctioning cells. 
 +  * OSKM () - activation and limitsno matter how much more activation occurs the cell does not reverse further. 
 +  * Other () - other unforeseen issues, such as mitochondria mutations (usually eaten by the immune system) on life-long non-replaced cells, DNA repair. 
 +  * Update() - ability ​to take second generation ovum and replace/​update the code.
  
-The theoretical Yamanaka therapy would be to add the Yamanaka factors somewhere in genome (they already exist in the genome, and we could just express them from where they are) along with the ability ​to express them. A switch to turn them on or turn them off. The switch to turn them on or off is activated by an unusual molecule that is taken orally. When the molecule is found the Yamanaka factors are expressed as the molecule dissolves they are no longer expressed. So that the person must take a tablet every interval allowing for short periods of expression and observation and then all clear and then take another. This therapy is not permanent but requires activation of the expression by the presence of some molecule or signal. It we do not turn off Yamanaka factor expression the person will die.+The largest other reason people want to do this is to make super intelligent humans. The Chinese government is working ​on this but it is more like eugenics.
  
-Yamanaka Factor Therapy has been tried in mice.+The companies at the forefront of human in vivo Yamanaka factor therapies are [[https://​turn.bio|Turn Biotechnologies]] and [[https://​youthereum.io|Youthereum Genetics]].
  
-That'​s ​a wrap, their are several companies with deep pockets working on the field, we may not know what they know. Their are many people who die every day and their are many people in a terminal state some conscious some not. Being sure to exclude psychopathic,​ moronic, sadistic, insane, invasive and painful procedures, they really have none to lose. It is important to note that aging is a downward cascade and age reversal is an upward reverse cascade. Daily or weekly sessions building the system up again. It probably starts with young blood (not plasma or major supplements but the real deal), the young blood allows for more physical activity which in turn makes the body build strength and so on. Secondly it has to do with the amount of cells aged people have to build, repair and replace existing cells. An I.V mixture of immune acceptable MSC's and haematopoietic stem cells so that the body can repair, replace and build its organs up using the supplemental cells and somewhere down the road triggering Yamanaka factors safely might come into play.+That is a wrap, we are out. I hope you have enjoyed the article. There are several companies with deep pockets working on the field, we may not know what they know. There are many people who die every day and there are many people in a terminal state some conscious some not. Being sure to exclude psychopathic,​ moronic, sadistic, insane, invasive and painful procedures, they really have none to lose.
regenetive_medicine_anti_aging_immortality.1590246518.txt.gz · Last modified: 2020/05/23 15:08 by admin