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  • The Anti-Aging Pill Story Is Getting Old

    April 12, 2021: by Bill Sardi

    It’s April 7, 2021 and Newsweek magazine posted up a review article about the state of anti-aging pills.  Any avid longevity seeker who has been following this story over time would have thought it was written over a decade ago.  The promise of an anti-aging pill is getting old.

    An anti-aging pill is always another decade away, another long-term controlled human trial, a conclusive meta-analysis providing compelling data to build a consensus of experts. But then again, that will never be enough.

    Since 2004 when Leonard Guarente at MIT and David Sinclair at Harvard published ground-breaking reports about small molecules when consumed orally can mimic the same genetic signal as a lifespan/healthspan-doubling calorie-restricted diet, the longevity genie escaped from the bottle.

    Here humanity stands 16 years after Guarente and Sinclair’s discoveries, and no scientist has changed his/her mind and totally dismissed resveratrol.  Resveratrol largely remains unapplied science.

    When a prolific researcher demonstrated resveratrol could pre-condition the heart so damage to heart muscle would be limited, that researcher’s papers were retracted and he was accused of scientific fraud even though other researchers conducted similar experiments with the same results.

    A recent scientific review published in the journal NUTRIENTS (Volume 12, page 1344, 2020) states:

    “Calorie restriction (CR) is the only non-genetic intervention that has evidence of prolonging the lifespan of model organisms from yeast to mammals. It protects against inhibition of biological functions by delaying or reducing the risk of many age-related diseases….However, most people would not adhere to such a strict CR diet program, therefore there is no doubt that it is advisable to search for natural and/or pharmacological molecules that mimic the effect of CR without reducing food intake, especially between the mid-age and old age. Such substances have become known as CR mimetics (CRM).”  Resveratrol is the most prominent and frequent CRM studied.  This has been demonstrated in humans.

    As such, molecules such as resveratrol (red wine), quercetin (red apple peel), fisetin (strawberries) induce an intracellular “self-eating” process, called autophagy, “to clean out damaged cells, regenerate newer, healthier cells.”

    No one made a mistake opting to take resveratrol pills, which remain a prime activator of the Sirtuin1 survival geneResveratrol is still referred to as the “holy grail” of Sirtuin survival genes.

    Curing the incurable

    Look at what happened when researchers used resveratrol among patients with thalassemia, an inherited disorder where the body doesn’t make enough or an abnormal form of hemoglobin, the oxygen-carrying protein in the blood circulation.  The result is severe anemia requiring repeated blood transfusions.

    In 52.2% of patients treated with resveratrol there was a complete cure (no further need for blood transfusions) and a partial response in 18.2%, with no response in 15.9%.  A year later this curative response was maintained.  This astounding study received no worldwide publicity.

    A resveratrol-based dietary supplement has restored functional vision to legally blind octogenarians after all other therapies had been exhausted.

    Resveratrol is curing the incurable! Yet resveratrol is not even among the top 100 herbal supplements sold.

    Short-half life: NOT

    Researchers incongruently argue resveratrol cannot be working because it (a) has a short half-life (14 minutes) and is not bioavailable (it is bound to detoxification molecules as it passes through the liver; and (b) yet resveratrol is metabolized in the liver (bound to sulfate or glucuronate) which prolongs its half-life to 9 hours.

    What researchers fail to recognize is that the enzyme glucuronidase, which is abundant at sites of infection, inflammation and malignancy, releases resveratrol from glucuronate as free unbound resveratrol at the site where it is most needed.  The claim that resveratrol is not bioavailable is totally bogus.

    More is not better

    Another misdirection is the idea that more resveratrol is better.  Low-dose resveratrol is an antioxidant (binds to copper) whereas mega-dose resveratrol promotes oxidation (releases copper).  Even low-dose resveratrol is initially pro-oxidant, which activates internal antioxidant defenses via the Nrf2 gene transcription factor to produce endogenous enzymatic antioxidants (glutathione, catalase and superoxide dismutase).

    Resveratrol exhibits a bi-modal dose-related effect.  At low-dose resveratrol inhibits cancer by its growth and inflammation inhibiting properties, anti-hormonal (anti-estrogenic) properties, and by boosting immunity.  At high dose resveratrol selectively destroys cancer cells, without damaging healthy cells.

    In one study low-dose resveratrol suppressed intestinal cancer development more potently than higher-dose.

    A relatively low dose of resveratrol partially mimics calorie restriction and retards aging in the animal lab.

    At low-dose resveratrol promotes health whereas at high dose it kills cancer cells.

    Resveratrol is known to have a hermetic response, that is, it is effective at low doses but toxic (cell killing) at high doses.

    Whereas plain resveratrol exhibits a pro-oxidant effect in mega-doses, a unique low-dose matrix of resveratrol, quercetin + IP6 rice bran maintained a protective antioxidant effect even when given in mega-doses (2800 mg human equivalent) that killed rodent hearts in the laboratory.  Thus Longevinex® is not toxic at both low and high doses.

    Via molecular synergism (resveratrol, quercetin, IP6 rice bran) Longevinex® is able to provide low-doses to achieve a greater effect.  The triple-molecule Longevinex® activated 9-fold more longevity genes than plain resveratrol at a low dose.

    Critique of Newsweek report

    Hopes for an anti-aging pill have been seemingly dashed numerous times over the past decade and a half.  But there have been milestone achievements.

    To continue with the critique of the NEWSWEEK report on anti-aging pills, excerpts of the Newsweek report are followed by short commentary.

    • “Blood from young mice had seemingly miraculous restorative effects on the brains of elderly mice.” – A story that began in 2011.  So old humans sew themselves to a young person to stay young like they do mice in the laboratory? 
    • “A growing number of other geroscience health startups signal a change in thinking about some of the most intractable diseases facing humankind. Rather than focusing solely on the etiology of individual diseases like heart disease, cancer, Alzheimer’s and arthritis—or, for that matter, COVID-19—geroscientists are trying to understand how these diseases relate to the single largest risk factor of all: human aging.” – Harvard gerogenetic biologist David Sinclair was unveiling this idea to the public back in 2004.
    • “Their goal is to hack the process of aging itself and, in the process, delay or stave off the onset of many of the diseases most associated with growing old.” Already accomplished back in 2008.
    • “The result is a flood of investment money, an explosion of research into what precisely goes wrong in our bodies as we get old and the promise of clinical results down the road.”Yes, but we learn, behind the curtains of anti-aging science is the political idea it can’t be allowed to happen until the world’s population declines.  The recent book EMPTY PLANET notes that human populations are in decline almost everywhere on the planet.  The fear of over-population is outdated.  North America, western Europe, Japan and Italy are all in steep population decline. 
    • “The National Institute of Aging, under its director, Richard Hodes, recently announced plans to spend about $100 million over the next five years on basic research aimed at understanding ‘cellular senescence’.” Already reported.  The small molecule fisetin derived from strawberries was found to be the most potent at halting and reversing cellular senescence.  There is nothing keeping the public from taking this molecule to curb the rate of aging.
    • “Although the vast majority of these efforts remain in preclinical development, several have recently entered FDA trials and could potentially hit the market in a few years. Some are already appearing on the gray market, raising concerns that hucksters are peddling anti-aging snake oil.” – Any natural remedy, regardless of the science that backs it, is considered snake oil, that is, unless an oligarch owns and patents it.
    • “Will poor young people be coerced into selling their blood to elderly billionaires? Will magical anti-aging pills become the province of the Park Avenue and Hollywood rich, like facelifts, hair plugs and botox injections? Will the rest of us senile peasants be forced to watch them age backwards as we are left to wither and die?” — Not if timid longevity seekers dig into the science and begin to realize an indefinitely long lifespan/healthspan is achievable today without breaking everybody’s bank book or sewing the circulatory system of young people together with old people.
    • “The first hint that hacking the biology of aging might be possible came, improbably enough, from a series of laboratory experiments on a lowly species of roundworm. In the late 1980s and early 1990s, studies of identical twins had already shown that about 30 percent of longevity in humans could be attributed to genetics.” – The talked-about researcher has been touting that worm experiment for almost three decades now.   If you have pet worms, follow her advice.
    • “Then in 1993, Cynthia Kenyon, a biologist at the University of California in San Francisco, doubled the lifespan of a worm from three weeks to six by mutating a single gene.  – Yep, that was 27 years ago.”  – Yes, precisely my point, why aren’t we activating an analogous gene in humans?
    • “When the insulin and IGF1 in humans or analogous compounds in worms are dialed down—because we are starving, or the genes have been tweaked—a host of cellular repair mechanisms that are normally on standby kick into high-gear.” – Yes, this is do-able today. 
    • “A third approach would increase the production an enzyme called AMP-Kinase, which modulates cellular processes like growth and metabolism, based on the level of energy available for consumption.” – Yes, all roads lead to AMPK.  The anti-diabetic drug metformin is considered king of AMPK activators.  Resveratrol activates the cell-energy-sensing AMPK 50-200 better than metformin.
    • “Much of the hardiness of the mole rats to an abundance of hyaluronic acid, a major component of skin that is involved in tissue regeneration. Although mice and humans also have hyaluronic acid, the tissues of naked mole rats are “saturated with it.” — Oral hyaluronic acid can be consumed; it stimulates fibroblast cells to make youthful levels of hyaluronan again.  We already know this.  Modern medicine believes in hyaluronan as it injects it in lips, knees, etc.  It ignores the fact oral hyaluronan is a regenerative molecule that can be taken orally.  Hyaluronic acid is already incorporated into nutraceuticals.
    • The differences between the mouse and naked mole rat are easily explained by evolution—their respective adaptations are geared toward increasing their chances of reproductive success. – The naked mole rat hasn’t evolved into long life.  It eats roots that contain small molecules that influence its genome and instruct the body to make more hyaluronan
    • “If you put this work in an evolutionary perspective, we were not supposed to live that long,” ……”Aging is an invention of mankind. No animal species has successfully cheated its own body—cheated nature—except mankind. Elephants may live for 100 years but they lived for 100 years a million years ago. Humans have outsmarted their own body.” — Balderdash!  Humans are devolving, not evolving.  Humans internally produced vitamin C generations ago and likely lived much longerCorrection of the gene mutation that halted the internal production of vitamin C has been achieved.  Humans could conceivably live three-times longer. 
    • “Whatever it was in the young blood that spurred the regeneration, it seemed unlikely it would be able to pass the blood-brain barrier, the semipermeable border that keeps circulating blood, and much of the cargo it carries, from entering the central nervous system.” – Increasing iron load in red blood is the problem.  Young blood is not iron-overloaded.  The ferritin iron storage number should be 20-90.  Blood letting or use of natural iron-chelators (fisetin, quercetin, rice bran IP6) would reduce ferritin levels.
    • “In the years since the initial mice experiments. . . . a number of independent investigators have identified an array of proteins that seem to have promising restorative effects—or, in the blood of elderly mice, detrimental effects.” – Primary problem is elevated blood sugar.  Conversion of glucose back to ascorbate (vitamin C) via correction of a gene mutation would be best approach.  Most mammals convert blood sugar to vitamin C.  Humans have a gene mutation and can’t do that.  This gene mutation has been corrected with an oral dietary supplement that is being ignored.
    • “A new class of “anti-aging” drugs called ‘senolytics,’ which aim to clear out ‘zombie-like’ senescent cells that accumulate with age, have entered trials.”  – Yes, fisetin, a natural molecule found in strawberries, was found to halt or reverse senescent cells in the body.  Don’t need to wait for a drug.
    • “For now, the only proven anti-aging cures remain what they have always been: regular exercise, a good night’s sleep and a healthy diet.” – Standard drivel doled out by modern medicine.  Stress is man’s biggest health problem.  Humans lost ability to handle stress when they lost the ability to convert glucose to ascorbate (vitamin C).

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