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Arrest Of Aging

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Successful inhibition of aging CANNOT be achieved by following the usual advice on the internet. As we will see, weird diets, frantic exercise, self-flagellation of every stripe, and most of the so-called anti-aging drugs and supplements, likely accelerate aging and disease. 

I am going to take you on a journey through some of the top aging research laboratories in the world, to explore the new discoveries of the last decade that will truly extend healthy human life. Most of these discoveries are not public yet and conceptually are beyond the reach of most media, mired as they are in obsolete science of the 20th century. 

Note that all the aging science of the last century failed miserably to increase maximum human lifespan by even one year. The multi-multi-million $$$ studies of rhesus monkeys by the National Institutes of Health also failed, (although the treated monkeys were healthier overall). 

Finally, during the last few years, scientists have bowed humbly to the old maxim: If you keep repeating the same failed work over and over again, do not expect a different result. Aging research has now turned to radically new concepts of the molecular basis of life, and we are rapidly learning how to manipulate controlling molecules that determine the multiple ways in which we age. It’s the most exciting time in my scientific life, and I have been studying aging for 55 years.

First, we have to know what aging is, and how it happens. In this post, I will give you a quick summary sketch, because several of the concepts may be new to you. Without a basic knowledge of them, however, you have no chance to take the necessary steps to extend your life.

CIRCADIAN CONTROL

  1. Human life is controlled primarily by light. Genetically in-built circadian clocks, triggered by melatonin in response to the 24-hour revolution of the Earth about its axis, run all physiology, even the microbiome, in a diurnal cycle lifelong.
  2. Light controls melatonin release from the pineal gland in response to signals from the light-sensitive suprachiasmatic nucleus (SCN) in the hypothalamus, in the center of the brain, to reset all clocks each 24 hours.
  3. Clocks can be disrupted and become out of synchrony with the diurnal rhythm by environmental inputs of modern life, including jet-lag, irregular eating schedules, artificial light, computer and cell phone use. About 70% of the US population has allowed these environmental inputs to desynchronize their circadian rhythm.
  4. Melatonin release genetically programs growth from infancy, and triggers puberty, then declines rapidly to an insufficient level to maintain the body after reproductive maturity, about age 35. After that age, having children becomes increasingly hazardous, and genetically programmed natural selection winds down its mechanisms that maintain life.
  5. Maintenance of melatonin level and resetting of circadian clocks daily, by use of exogenous melatonin at night, and by lifestyle habits that match the circadian cycle, is the first essential strategy to prolong healthy life and to maintain cognition. Melatonin pills, however, generally do not work as they are destroyed by digestion and first pass through the liver. Recent developments have produced effective melatonin supplements in the US and in Europe that enter the human brain. We have used these in our arrest of aging research with human subjects for the last 8 years. They are not the complete answer to the genetically driven decline of the melatonin system, but, in conjunction with specific lifestyle changes, they are the first essential step to arrest aging.

EPIGENESIS

  1. The second step after circadian control is control of epigenesis. From conception on, though your DNA remains unchanged, environmental inputs progressively change the proteins made to each DNA code. That is why the popular commercial sequencing of individual genomes is almost totally useless.
  2. Millions of changes every day in your proteins, changes that cannot be predicted from your DNA, produce the epigenome, the total operating system of your body that supports its growth and development (until reproductive maturity). This is the “Me” that you see in the mirror every morning.
  3. After reproductive maturity (about age 35) the epigenome develops a progressive degenerative phenotype that gradually drives senescence.
  4. The degenerative phenotype of aging can now be partially reset to a younger age, by selective dedifferentiation of molecular phenotypic changes.
  5. Without, first, maintenance of the melatonin rhythm and second, selective dedifferentiation of the phenotype, the usual rate of aging cannot be changed. Yet these overriding controls are hardly even mentioned in the media.

CONTROLLING GENES

  1. To reset the aging phenotype requires manipulation of controlling genes and linked pathways that determine millions of downstream operations of proteins each second of life. 
  2. The controlling genes and pathways most researched are:
    1. insulin
    2. insulin-like growth factor -1 (IGF-1)
    3. IIS pathway
    4. d. phosphatidylinositol P3 kinase (Pl-3K)
    5. ribosomal protein S6 kinase (p70S6K)
    6. mechanistic target of rapamycin (mTOR, mTORC1, mTORC2)
    7. nuclear factor kappa-B (NF-kB)
    8. silent-information regulators 1, 3, and 6 (SIRT1, SIRT3, SIRT6)
    9. protein kinase B (AKT),
    10. forkhead-box transcription factors (FOXOs)
    11. k. adenosine monophosphate-activated protein kinase (AMPK)
  3. Manipulation of these genes and pathways has now been shown repeatedly to inhibit degenerative diseases linked to aging and to extend maximum lifespan in animals, including mammals who have near identical systems to our own.
  4. Recent clinical trials also show reversal and complete cure of various cancers by manipulation of these genes.

mTOR

  1. The mTOR gene and its pathways control all protein synthesis. Because every working unit in your body is a protein, the most important gene to work on is mTOR. It is the focus of our arrest of aging research.
  2. After reproductive maturity (age 35), mTOR becomes progressively deregulated, likely by decline of the melatonin system. This deregulation is now strongly linked to age-related diseases, including atherosclerosis, the metabolic syndrome, cancer, and neurodegeneration.
  3. After age 35, deregulated mTOR begins to block manganese superoxide dismutase, a major antioxidant protector of the mitochondria. This action alters the balance of redox control, allowing excess production of reactive oxygen species. Unless we manipulate mTOR to prevent this change, every part of your body fills with oxidative stress that drives multiple diseases. You cannot prevent this happening by taking nutritional antioxidants.
  4. After age 35, deregulated mTOR also begins to block autophagy, the major house-cleaning mechanism in your body. Blocking autophagy prevents the body from eliminating harmful molecules, toxins, viruses, and misfolded proteins, (such as amyloid-beta, which is strongly linked to Alzheimer’s.
  5. Note that the galloping rate of Alzheimer’s and other dementias, plus dementias caused by strokes, together are now the fourth leading cause of death. Maintaining autophagy by judicious inhibition of mTOR, is a big player in arrest of aging, yet most people do not even know what mTOR or autophagy are.
  6. After age 35, deregulated mTOR also begins to block the translation phase of the cell cycle, leading to disordered protein deposition, now considered to be a major cause of Alzheimer’s, stroke, and a raft of other diseases.
  7. All known mechanisms in deregulation of mTOR during aging can now be partially reversed by judicious inhibition of mTOR and its pathways.
  8. Effective forms of well-known drugs and natural compounds are now being used in research and experimental medicine to achieve effective inhibition of mTOR and its linked genes and pathways, especially in treatment of cancer.
  9. Used correctly, the most effective drugs that inhibit deregulated mTOR are: 
    a. Aspirin, 
    b. Metformin
    c. Rapamycin (sirolimus) and its analogs.
  10. The twelve most effective botanicals and natural compounds, legal in the US, which have recently been used successfully to inhibit deregulated mTOR, in both research and clinical trials, are:
    a. Melatonin
    b. R+ lipoic acid
    c. EGCG 
    d. Resveratrol 
    e. Curcumin 
    f. Sulforaphane 
    g. Berberine
    h. Hyaluronic acid
    i. Silibinin
    j. Coffee polyphenols
    k. Oleuropein aglycone 
    l. Vitamin D3 One caution. As we will see in a further article, although effective when injected and in specific nanoparticle formulations now used in experimental medicine, most botanicals sold as pills, powders, or liquids are extremely resistant to absorption and use by the body. From tests in our lab and others, absorption is negligible (less than1%), for about 90% of all the botanical supplements sold in health food stores.
  11. Compounds which increase deregulation of mTOR, but are also essential to maintain muscle mass with aging are:
    a. Whey protein
    b. BCAAs
    c. Leucine
    d. Arginine
    e. Carnosine
  12. Effective arrest of aging has to create a balance between mTOR stimulation and inhibition.
  13. Mechanisms of cancer development and mechanisms of aging have proved to be so similar, that numerous experts are now advocating the re-classification of aging as a disease, therefore allowing medical insurance claims. This reclassification is to be presented to the Eleventh International Classification of Diseases (ICD-11) expected to be finalized in 2018 and to come into law in 2020. Should this occur, many of the above points I have noted will suddenly become big news.

I have given you just a very brief summary of the latest in aging research. Over the next few weeks, I will present articles on each point, complete with peer-reviewed references and quotes from some of the leading scientists in the world. I hope you will read them and that you will ditch the mish-mash of nonsense on aging that currently pervades the media. If you do, I am confident you will lead a longer and healthier life.

Dr. Colgan is an internationally renowned research scientist. He is acknowledged as one of the world's most popular scientific experts in nutrition, exercise and the inhibition of aging. At age 75, he is a living example of the power of nutritional science to maintain lean and vibrant health. From more than 50 years of aging research, and from training many world champion athletes, he brings a unique understanding of environmental toxins and how to combat them.
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