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  • Three Pathways To
 Super-Longevity Emerge

    December 5, 2016: by Bill Sardi

    Blood plasma exchange from old to young, modified versions of calorie restriction and a third new approach to super-longevity have emerged in the past year. Humans now have instruction how to achieve an indefinitely long lifespan.

    Short of having surgeons intertwine your organs and blood vessels with another younger individual in an intervention called parabiosis that was previously shown to improve health and prolong life of laboratory animals, researchers recently infused blood plasma from young adult humans into to old mice which resulted in a similar dramatic rejuvenation of the body and brain.  New cells were created in the hippocampus, the thinking lobe of the brain.  Researchers describe young blood plasma as having a “massive rejuvenating effect.”  [Daily Mail Nov 15, 2016]

    Is humanity on the cusp of having young people earn their way through college, being paid to donate their blood plasma to youth restoration centers for infusion in senior adults?  It sounds like that may not be too far off in the future.

    The malignant spirit that accelerates aging in old blood may not be an unknown factor.  [Ageing Research Review Jan 2003] It won’t be too surprising to find it is excess iron in old blood that accelerates aging.  About 65-70% of the body’s iron is bound up in the red hemoglobin pigment of red blood cells.  Each unit of whole blood contains approximately 200-250 milligrams of iron.  The adult human body contains ~3000-4000 milligrams of iron.

    A standard blood test measures the level of iron in blood plasma (not red cells).

    Misleadingly, some older adults may be anemic (~10% at age 65 and double that at age 85), but giving them more iron may kill them.

    Anemia in the elderly is often not due to lack of iron in the diet or poor absorption of iron but rather due to the binding of dietary sources of iron.

    More specifically, iron is bound to iron-binding proteins (ferritin or lactoferrin) in states of chronic inflammation or infection that characterizes aging.  In this state, there is an increased amount of bound iron (ferritin, lactoferrin) but little that is being released in bone marrow to make new red cells in bone marrow. [Mechanisms Ageing Development March 2014]

    The body withholds iron as a self-protective mechanism since iron is utilized for tumor cell growth and growth of germs.  When there is chronic inflammation or infection, iron is bound to a protein called ferritin.  High ferritin levels may indicate iron overload or may indicate there is chronic inflammation/infection.

    Elderly adults who consume a western diet are more likely to have high iron stores.

    Blood donation has been shown to improve survival of adults age 50-70 years, but not thereafter.  [Vox Sanguinis 1983] Frequent blood donation increases life expectancy. [Transfusion Oct 2015]

    Bottom line, it may not be calorie restriction per se that prolongs life but the fact iron stores are reduced when calorie restricted diets are put into practice.  [Journal Neuroscience Aug 22, 2012; Journal Neuroscience June 9, 2010]

    I have written how periodic blood donation for middle-aged males and non-menstruating females would cost far less (nothing) than costly drugs and the need to purchase expensive health insurance plans.  A pint of whole blood donated every 56 days or 6 pints of blood a year, eliminating 250 milligrams of iron per unit of blood (1500 mg total) would boost healthspan and lifespan. [Knowledge of Health]

    Blood plasma exchange, called apheresis, is not new.  Apheresis is practiced, but not commonly.  It has application for a broad number of maladies.  [Journal Clinical Apheresis Feb 2013] Apheresis replaces albumin, an iron-controlling molecule in itself.  Red blood cell apheresis can also be performed to effectively reduce iron stores without blood letting. [Transfusion May 2015]

    Short of receiving young blood in place of old, blood donation represents an anti-aging strategy.  Iron and heavy metal chelation is another.

    Aside from blood exchange or donation, what can be done to achieve superlongevity?

    Two emerging life prolongation strategies

    Newly published reports point towards two pathways to superlongevity as evidenced now in animal and human models.

    For the first time longevity seekers have a choice of aiming at an approach to life extension that could result in: (1) 120-150 healthy years of life or (2) produce an indefinitely long lifespan.

    Stratagem #1

    The first of these pursuits is more familiar to longevity seekers and is known as calorie restriction (CR), which was historically preceded by fasting.

    In the distant past CR was practiced by Luigi Cornaro who lived from 1464 to 1566 AD in Padua, Italy and was declared a glutton and a drunkard by his physicians at the age of 35.  From that point in time forward Cornaro consumed only 12 ounces of food and 14 ounces of red wine daily.  (Only an Italian would think the equivalent of 3 glasses of wine is modest consumption.)  [The Art of Living Long]

    The red wine was unfiltered at the time and provided 30 times more molecules called polyphenols (resveratrol, quercetin, gallic acid, others) than filtered wine today.  Polyphenols are molecular mimics of a limited calorie diet, that is, they activate the same genes as a sparse calorie diet.

    Cornaro went on to write a meticulous account of his long life.  He was jumping up on horses and singing songs in his 90s.  He died in a rocking chair at age 102 years.

    The most recent example of CR is the account of Emma Morano of Verbania, Italy, the oldest person at age 117 years at the present time.  She says her secret to living across three centuries has been “not eating much.”  But food intake has been limited not because she wants to practice calorie restriction and live longer but because “I have no teeth,” she says.  She is edentulous.  For a long time she is reported to have eaten nothing more than 3 eggs a day and a few vegetables.  [The Guardian Nov 28, 2016]

    Her memory is intact as she recalls events that date back more than seven decades.  [The Guardian Nov 28, 2016]

    Of course, we are not to conclude from this that dentists should universally pull teeth from every aged adult.

    It was Clive MacCay at Cornell University in the 1930s who first showed that food restricted spiders lived longer.  Since then CR has been demonstrated to double the lifespan and healthspan of most forms of life. [Journal Nutrition July 2010]

    The advantages of a calorie-restricted diet are obfuscated by those in the scientific community, which ignores published science.  In laboratory mice, over a short-term of 12 weeks, a so-called red wine pill added to their diet activated 82% of the same genes (677 or 831 genes) triggered by a life-long calorie restricted diet, but that striking report has largely been closeted.  [Experimental Gerontology Sept 2008]

    Follow-up studies reveal intermittent food deprivation (16 hours or more to use up all the energy stored in the liver which switches the body to using stored fat for energy) may produce similar health benefits to daily calorie restriction making the benefits of CR a more achievable practice.  [FoxNews Sept 14, 2016; Ageing Research Reviews Oct 31, 2016]

    Stratagem #2

    The second longevity stratagem can be described as the connective tissue theory of aging.  It may be new to longevity seekers.  It is characterized by the naked (hairless) mole rat that lives underground in burrowed tunnels and in the wild has never been reported to develop cancer.  The naked mole rat lives 10 times longer than other rodents (30 years instead of 3-4 years).  [Journal Gerontology A Nov 2005; Institute of Laboratory Animal Resources Journal 2011]

    The secret of this animal’s superlongevity has only recently been uncovered.  Naked mole rats exhibit intact connective tissue throughout life, as measured by analysis of hyaluronic acid (HA).  Hyaluronic acid is a gel-like water-holding, space-filling molecule that is produced in the goo that lies between cells, called connective tissue.  [Nature July 18, 2013]

    The cosmetic aspects of this molecule in producing smooth wrinkleless skin and thick hair have been underscored.  HA is injected into lips, brows, and joints by dermatologists and orthopedists to eradicate wrinkles and lubricate joints.  It is the molecule of youthful appearance and function.  It is also a longevity molecule.

    Only recently has it been reported that the naked mole rat maintains intact hyaluronic acid by virtue of its ability to inhibit breakdown enzymes (hyaluronidase, metalloproteinase and nagalase) that cause it to fragment. [Nature July 18, 2013]

    Once fragmented, hyaluronic acid can no longer hold surrounding cells (called the microenvironment) in place.  Malignant cells can migrate to obtain nutrients and get into the blood circulation where cancer cells then spread to distant organs (called metastasis) and become life threatening.

    Cancer is an age-related phenomenon.  In youth humans produce abundant amounts of hyaluronic acid.  Cancer rates are low in youth and increase with advancing age.  Lifetime accumulation of iron and other metallic minerals may explain why breakdown enzymes of hyaluronic acid become more active with advancing age.

    The Yuzurihara phenomenon

    I wrote a book entitled How To Live 100 Years Without Growing Old [] that told of a population of people in the village of Yuzurihara, Japan that was designated as the oldest living population in that country by the World Health Organization.

    Dr. Toyosuke Komori the town doctor wrote books that described this long-living population as having low iron diets and high levels of hyaluronic acid.  [ABC News Prime Time Live]

    Residents of Yuzurihara, where I visited, were physically active into their 8th and 9th decade of life, growing their own food and maintaining their independence.  Fish from a local stream comprised the meat in their diet.  Some aged Yuzuriharans could read fine print without reading glasses.  They exhibited flexibility rather than the characteristic stiffness of old age.

    As a guess, Yuzuriharans youthful longevity was attributed to sticky vegetables in their diet, but after having eaten their traditional food at the town center I believed it was the fermented soy.  Concentrated phyto-estrogens in foods like miso soup and tempeh combined with their low iron diet could be responsible for their youngevity.

    Estrogen and hyaluronic acid

    Supplemental estrogen activates fibroblast cells to naturally produce hyaluronic acid in the body, which is why women have smoother skin, thicker hair and greater flexibility than males.  [American Journal Obstetrics Gynecology April 2008; Therapie Jan 1996; Biochimica Biophysica Acta April 1981] Females also live longer.   Menopausal women have been unduly frightened away from estrogen replacement therapy by the medical establishment. [Journal American Geriatrics Society June 2013]  In lieu of estrogen replacement, resveratrol is the safest plant estrogen. []

    For reference, resveratrol, quercetin and catechin along with other polyphenolic molecules in wine, tea and coffee are classified as phyto (plant)-estrogens.  They have weak estrogen-like qualities.  These molecules also inhibit hyaluronidase the HA breakdown enzyme.

    Very recently it was discovered that the naked mole rat living in the wild consumes a hefty amount of polyphenols from roots and tubers, which serve as enzyme inhibitors.  It is the enzyme inhibition that maintains intact hyaluronic acid in the naked mole rat.

    Only recently has it been reported that a few cases of cancer in naked mole rats living in a zoo, separated from their polyphenolic-rich diet.  [Journal Gerontology A April 29, 2016] This suggests its cancer-resistance can be controlled via dietary measures and is not inherited.

    Cancer cell environment

    It was Mary Helen Barcellos-Hoff at the University of San Francisco who demonstrated the importance of maintaining the microenvironment surrounding living cells in the body in order to prevent cancer.

    Barcellos-Hoff took healthy breast cells and removed them from their gooey connective tissue matrix and then zapped the remaining connective tissue with radiation.  Then the healthy breast cells were replaced within this matrix.  While never themselves exposed to radiation, the cells rapidly became malignant and metastatic, thus demonstrating the importance of maintaining connective tissue integrity to prevent cancer. [Cancer Cell May 17, 2011;]

    The connective tissue theory of aging moves into the human arena with reports coming from Europe of the use of gc protein macrophage activating factor (gcMAF) in quelling cancer in human subjects.

    gcMAF is naturally produced in a healthy human body as an activator of cancer-killing white blood cells known as macrophages.

    gcMAF: private enterprise moves ahead

    In regard to gcMAF research, private enterprise appears to be moving faster than the National Institutes of Health that funds most of the cancer research throughout the world.

    Researchers affiliated with Immuno Biotech on the Isle of Guernsey in the British channel have successfully treated hundreds of cases of terminal cancer with gcMAF.  [Oncoimmunology Aug 1, 2013]

    Reports of this have been squelched by the news media.

    I have personally witnessed a 53-year old man with pancreatic cancer who had been on oral chemotherapy with little or no benefit who experienced rapid remission of his stage 4 pancreatic cancer within six weeks of using gcMAF.

    GC protein is produced in the liver and after having a couple of sugar molecules knocked off it becomes gcMAF.

    Immuno Biotech has extracted gcMAF from human blood plasma donated from healthy subjects and provided it to otherwise hopeless cancer patients as an injectable blood fraction (it is not a dietary supplement or a hormone).

    Macrophage activation or hyaluronic acid stabilization?

    The macrophage activation of gcMAF has been over emphasized.  Yes, gcMAF activates sluggish white blood cells known as macrophages to literally digest and engulf cancer cells.  This would be more applicable to treatment of non-solid tumors such as cancer of the blood (leukemia) and lymph (lymphoma) where macrophages are abundant.

    However, its chief action is to inhibit nagalase, an enzyme that breaks down hyaluronic acid and facilitates the growth of solid tumors.

    Now a connection has been made between an unusually long-living cancer-proof animal, the naked mole rat, and human cancers that have been cured in a few hundred patients with injection of gcMAF.

    This suggests humans who consume ample amounts of polyphenols (caution, there are side effects from over-dosing) can theoretically become cancer proof and thus live far beyond what any human could possibly imagine.

    Hyaluronic acid not orally absorbed?

    A denial by modern medicine is that oral hyaluronic acid is not absorbed and therefore must be injected, either as a cosmetic skin filler or joint cushioning agent.  However, oral hyaluronic acid IS orally absorbed and not only provides a fresh supply of HA but activates cells known as fibroblasts to produce more HA.  This became evident in an experiment where HA was injected into the knee and more HA was found in the tissue than what was injected.

    Imagine a nutraceutical

    Now imagine a nutraceutical comprised of hyaluronic acid + enzyme inhibiting polyphenols [Longevinex® Advantage].  Such an approach could mimic what is going on biologically in the naked mole rat.

    Live how long?

    It would be preposterous at this point to presume humans could live 10 times longer than they do today — 700 years or more as the naked mole rat does. Conclusive evidence of this is beyond reach as it would require many decades to prove.  But there is scientific confirmation that there are biological mechanisms that can be utilized to achieve an indefinitely long lifespan.

    Hormesis: mild biological stressors

    An overlay to these two approaches to superlongevity is hormesis, the exposure to mild biological stressors that activates the body’s internal antioxidant defenses.

    While there has been criticism that oral antioxidant therapy has been ineffective, activation of the body’s internal enzymatic antioxidants (glutathione, catalase, superoxide dismutase) via the Nrf2 gene transcription switch is far more powerful than swallowing antioxidant pills.  [Current Opinion Clinical Nutrition Metabolic Care Jan 2011]  Chinese Journal Physiology Feb 2015]  Polyphenols abundant in red wine and provided in concentrated form in dietary supplements are activators of the Nrf2 antioxidant switch. [Molecular Neurobiology Oct 2011]

    Every cell in the body can produce these antioxidants, thus placing the body in a defensive mode that blunts injury to living tissues in the heart, brain, kidney, liver and elsewhere should an adverse biological event (blockage of blood circulation to the heart or brain – strokes or heart attacks) occur.  This phenomenon is called preconditioning.  [Molecular Cellular Biochemistry Jan 2014]

    While, for example, environmental exposure to low-dose terrestrial radiation (radon) or mild solar radiation (vitamin D) may activate internal enzymatic antioxidants that characterize hormesis, there are molecules in the diet such as resveratrol, quercetin (wine), catechin (tea), allicin (garlic), caffeic and chlorogenic acid (coffee) that when consumed initially promote oxidation and provoke hormesis.  Habitual consumption of these molecules keeps the body in a biological defensive posture.

    Could the long-living Biblical patriarchs like Noah who fasted and drank wine have actually tapped these biological mechanisms?

    Society not prepared to move ahead but individuals can

    Since modern societies are in no way prepared or able to provide medical care and retirement checks to large numbers in their population, life-extension technologies will be shunned or repudiated.  It will be every man for himself.

    The State is not likely to underwrite or lend its imprimatur to so-called anti-aging pills.  Individuals will have to bolt from the pack and practice superlongevity strategies on their own.

    Can you imagine going to a doctor to get a prescription because you have been diagnosed with premature aging?

    Aging involves many genes, 831 in mice.  Modern gene-targeted drugs influence a narrow set of genes, too small to molecularly mimic any known model of aging.  So-called promiscuous molecules found in nature like resveratrol that control hundreds of genes are miles ahead of any synthetically made molecules being tested to slow aging. [Annals New York Academy Science Aug 2015]

    Modern medicine is in denial as thousands of resveratrol pill users have benefitted in a myriad of ways.

    The biology community went so far as to falsely accuse a leading resveratrol researcher of scientific fraud.  Sales of resveratrol pills plummeted worldwide.  Yet his work was corroborated by research studies from independent researchers in Canada and Italy. []

    We must not overlook the fact modern medicine discards those incredulous discoveries it can’t turn into a profitable venture.

    As an example, cancer-proof mice were also discovered by researchers at Wake Forest University.  These mice had very active neutrophils, another type of white blood cell that kills cancer cells.  A subsequent evaluation of university students blood samples found many students who exhibited the same resistance to cancer as the cancer-proof mice.  But the students only exhibited this cancer resistance in the summer, which suggests sunshine vitamin D was responsible for the heightened neutrophil activity.  Because vitamin D could not be commercialized to product a blockbuster drug, further studies were abandoned.  []

    Biologists and geneticists have essentially said “don’t do anything until we prove this scientifically in a controlled study.”  However, conclusive evidence that certain health practices produce superlongevity would require 8 to 10 decades or more, or if effective in reversing aging when introduced later in life, such as at age 50 or 60, would still require a few decades to be proven.

    Those longevity seekers who are over age 50 haven’t the time to wait for science to sort this out.

    The disease care-oriented health system has run into its own dead end as it is no longer affordable and fails to address many of the new challenges posed by aging such as loss of muscle mass (sarcopenia), diminished eyesight (macular degeneration), mental decline (dementia), sensory hearing loss, shrinkage of glands and accompanying decline in hormone secretion (estrogen, thyroid, insulin, thymulin), and collapse of the body’s skeleton and connective tissue.

    Dissatisfaction with conventional and alternative medicine

    Given a choice between conventional and alternative medicine, how about none of the above?

    Dissatisfaction with modern medicine and alternative medicine is growing.  Ineffective therapies that comprise alternative medicine, namely alkaline diets proposed to cure cancer, have also left desperate patients wanting.

    Ouija-board alternative medicine and its homeopaths and chiropractors have had adequate opportunity to prove their approaches in the medical marketplace.

    Death rates from cancer and heart disease are reportedly tumbling but these reports are sometimes nothing but statistical manipulation (detecting cancer earlier and then saying patients are living longer while they are still succumbing to cancer on the same calendar day).

    Or a decline in mortality rates is falsely attributed to armaments of modern medicine such as statin drugs that have never been shown to reduce the occurrence of mortal heart attacks.

    The fact that the biological action of most prescription drugs can be replicated with amino acids, vitamins, minerals, omega oils and herbals cannot be hidden forever.  It has only been crony capitalism and fascism (buying off of government and the news media) that modern medicine has kept the prospect of an anti-aging pill out of the public’s view.

    Not to dismiss their non-invasive practices entirely, homeopathic and chiropractic practitioners have not contributed to any alleged drop in mortality rates.  In fact, it could be an increase in wine drinking that has produced longer-living human populations!  []

    Even personalized medicine utilizing genetic predispositions is rapidly exposed as archaic next to the emerging field of epigenetics and molecular medicine.

    This is an exciting time for humanity because the scourge of death is being pushed further and further into the future for many people.

    Many Americans are now living into the ninth decade of life and beyond, though often over-medicated and experiencing loss of independent living.

    Aging populations pose challenges that modern society is structurally and financially unprepared to address (pools of funds for medical and retirement plans will be depleted).

    At some point the financial and personal burden of caring for aged family members may expose the folly of attempting to treat each and every malady of aging (cloudy cataracts, heart failure, cancer, nervous system decline, kidney and liver failure, etc.) in favor of an approach that addresses the aging process itself.

    Individuals who have chosen to practice molecular medicine on their own by habitual use of nutraceuticals such as fish oil, amino acids such as leucine and taurine, lettered vitamins, trace minerals, mineral chelators derived from rice bran and polyphenols such as quercetin, resveratrol and catechin, are delaying aging.

    A very few individuals have lived to age 115 years or more.  They achieved superlongevity by happenstance.  They were not intentionally attempting to live longer.  This is the first generation that has an opportunity to consciously attempt to live 120 years and beyond in good health.

    Chart: Projected Survival of Anti-aging-pill users

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