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How the world got lost on
the road to an anti-aging pill
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March 28, 2017: by Bill Sardi
Want to achieve superlongevity as the Biblical patriarchs were reported to have achieved? Lengthen your telomeres (end caps on chromosomes) say some scientists.
Want to live an unlimited lifespan? Switch on a family of survival genes known as Sirtuins. Resveratrol pills do this.
Deprive yourself of food. Eat only one modest meal a day and go hungry most of the time. This same dietary practice doubled the healthspan and lifespan of laboratory animals and likely does the same for humans.
But when we step “backstage” and peer behind the curtains on the biology stage we find that chelators (key-lay-tors) that cleave to minerals and halt the life-long accumulation of minerals is what reverses biological aging, lengthens telomeres, activates survival genes and explains why calorie restriction by virtue of limiting intake of minerals results in remarkable longevity.
While there are many theories as to what causes aging (the mitochondrial theory, the antioxidant theory, the wear-and-tear theory, the hormonal theory), whatever does cause aging is not in play during the growth years, gradually increases thereafter and levels off in old age.
The only plausible explanation for the three speeds of aging is the overmineralization theory, which is captured in the following graphic.
Source: Iron homeostasis in health and disease, International Journal of Molecular Sciences 2016.
A dozen years ago (2007) I wrote the OVERMINERALIZATION THEORY OF AGING, which postulated that during youth minerals were in short supply. Calcium from the diet was being directed to grow bones; copper to make connective tissue and iron to make millions of red blood cells every second. With the cessation of growth (~18 years of age), minerals begin to accumulate. Females are spared the adverse consequences of overmineralization by donating calcium to their babies and dumping iron once a month during menstruation (akin to blood letting).
Full grown males however progressively accumulate calcium and iron and by age 40 have four times as much calcium and twice as much iron stored in their bodies compared to equal-aged females and subsequently incur a doubling of the rate of diabetes, cancer and heart disease.
Women who undergo an early hysterectomy suffer the same rate of disease as males. As women enter menopause they cease secreting estrogen from their ovaries and begin depositing calcium from their bones to their arteries.
Women begin to accumulate iron later in life than males (around age 42-51 years of age). [Antioxidant Redox Signaling Dec 2009] The recent observation that women whose last birth was after age 40 are more likely to live longer is consistent with the donation of minerals to offspring and the prolongation of life of the mother. [Journal Perinatal Medicine July 21, 2016]
Iron overload is a prevalent health problem. A convincing population comparison was conducted among men over age 74 in northern Europe (Zutphen, Netherlands) and the Mediterranean area (Isle of Crete). Men on Crete live a number of years longer than men in The Netherlands. The men living in Crete have an iron storage number of 69.8 (20-70 is a healthy range) versus 134.2 for men in The Netherlands. [European Journal Cardiovascular Prevention & Rehabilitation Aug 2007] To retranslate the above study in more meaningful terms, the entire adult male population in The Netherlands is iron overloaded.
Basically, humans calcify and rust as they age. Those who consume diets rich in calcium (dairy products) and iron (red meat) age faster.
Telomere length is a sideshow in biology. Shortened telomeres simply indicate a high state of oxidation and inflammation in the body. Lengthening telomeres will not prolong human life.
In the words of researchers: “Centenarians and their offspring are able to maintain long telomeres, but telomere length is not a predictor of successful ageing in centenarians.” [EBioMedicine July 29, 2015]
Indeed, the trace mineral selenium lengthens telomeres while lead accumulation shortens them. [Biology Trace Element Research Sept 2004] It follows that individuals taking iron supplements experience shortening of telomeres. [Environmental Toxicology & Pharmacology Nov 2015]
To summarize, telomere length is a marker of aging, not a governor of longevity. [ResveratrolNews.com Sept 4, 2014]
Loose metals (called free metals, i.e. free iron, free copper) not attached to binding proteins cause metal-induced oxidation, inflammation and tissue damage. So it follows that it is not reduced calories that produces the lifespan doubling effect of calorie restricted diets but rather the iron, copper and calcium that are not consumed.
For example, a calorie-restricted (CR) diet slows iron accumulation in the brain and preserves motor function in animals. [Journal Neuroscience Aug 22, 2012]
In another recent study researchers gave a sugar (galactose) to lab animals to accelerate brain aging but when combined with calorie restriction (CR) there was almost no learning or memory impairment. Researchers identified the underlying protective mechanism as the ability of the calorie restricted diet to control iron. Researchers concluded: “the anti-aging effects of CR might partially lie in its capacity to avoid age-related iron accumulation in the brain.” [Rejuvenation Research Feb 2014]
It is no surprise to learn that slowing calcification of tissues extends the lifespan of genetically altered mice. [Kidney Blood Pressure Research 2016] The greater the deposition of calcium in coronary arteries, the greater the increase in mortality. [American Journal Cardiology May 1, 2015]
There is less deposition of calcium in coronary arteries in offspring of long-living families. In one study the coronary arteries of 34% of men and 70% of women from long-living families had low calcium artery scores compared to men and women from control groups that only had 21% (men) and 54% (women) who had low calcium artery scores. Men and women with a familial propensity to become long-lived have lower coronary artery calcium scores than controls. [Age 2014]
It follows that individuals with calcium kidney stones tend to have high calcium artery scores. In a recent study, 47% of men and 69% of women with kidney stones had detectable calcification in their coronary arteries. [Journal Urology April 2016] Modern medicine treats kidney stones like they are an isolated problem. Kidney stones are a sign of aging. The bones are withering, calcium is being excreted and forms stones in the kidneys.
In a misdirection menopausal women are instructed to take calcium supplements which is like pouring calcium into a barrel with a hole in the bottom. Calcium supplementation in menopausal women results in more calcium being deposited in arteries. Arteries then stiffen.
The provision of replacement estrogen or resveratrol, the latter which exerts 1/7000th the activity of estrogen, restores the estrogen signal to hold calcium in bones. Resveratrol has been shown to remarkably restore bone volume and strength even in old laboratory animals that had already lost bone mass. [Rejuvenation Research Oct 2014]
Resveratrol has been shown to prevent age-related bone loss via its indirect ability to control iron. [Journal Nutritional Biochemistry Nov 2016] Resveratrol prevents age-related bone loss without activation of estrogen-sensitive tissues. [Annals New York Academy Science Aug 2016] Resveratrol protects bone integrity in males too. [Journal Clinical Endocrinology Metabolism Dec 2014]
Other natural anti-calcifying agents are vitamin D, vitamin K and IP6 phytate along with resveratrol are posed as a novel combination to slow or even halt age-related bone loss. [Minerva Ginecolica Oct 2014]
A published report elucidates the ability of metals to influence the dynamic aspect of turning genes on or off (called gene expression or gene silencing). [Journal Applied Toxicology 2012] Yet much of the credit for resveratrol’s life-prolonging effects are attributed to genes like Sirtuin1. However resveratrol activates Sirtuin1 by virtue of its ability to chelate copper. [Oxidative Medicine & Cellular Longevity 2017]
The red wine molecule resveratrol is the most studied metal chelator (key-lay-tor) in relation to aging. But 12 years after resveratrol was extolled on the front page of The Wall Street Journal as an anti-aging elixir that molecularly mimics a calorie restricted diet and activates the Sirtuin1 survival gene that is also switched on by a limited calorie diet, little mention is given to resveratrol’s demonstrative control over minerals, in particular copper.
There has been so much fascination with resveratrol’s ability to control anti-aging genes that its ability to restore a proper zinc/copper balance has been overlooked.
In an experiment where animals with chemically induced diabetes were given a modest dose of resveratrol, in addition to increases in nitric oxide and the enzymatic antioxidant catalase, resveratrol increased zinc concentrations and decreased copper induced oxidation of lipids (fats). [Biology Trace Element Research Sept 2007] A balance between copper and zinc is critical for human health, particularly immunity.
Resveratrol is a very strong copper chelator and does not chelate iron. [Biochemical Pharmacology May 9, 1997]
A common feature of aging is an increase of copper over zinc. [Mechanisms Ageing Development Nov 2015]
The ratio of copper over zinc is associated with inflammation. The blood plasma copper/zinc ratio increases with advancing age. [Biogerontology June 2010] Individuals with high copper/low zinc ratios tend to be plagued by chronic inflammation. [International Journal Medical Sciences 2013] Aging has been described as “inflammaging,” that is, low-grade chronic inflammation.
Some of the benefits of mineral chelation therapy can be simply duplicated by supplementing the diet with rebalancing zinc. [May Medical Hypotheses 2016]
As living cells in the body age they begin to lose their ability to divide and replicate. Resveratrol slows cell senescence by virtue of its ability to control copper. [Oxidative Medicine & Cellular Longevity 2017]
The failure to recognize the importance of the zinc/copper ratio may explain the mixed result studies involving resveratrol. Of note, obesity apparently lower zinc levels, which alters the synthesis of zinc-copper SOD (superoxide dismutase), an endogenous antioxidant enzyme. [Annals Nutrition Metabolism 2016]
Even in simple forms of life like yeast cells (Saccharomyces cerevisiae) calorie restriction activates copper and iron transport genes resulting in a decline of these metals inside living cells. [Molecular Biosystems Feb 2011] The yeast cells live longer.
A calorie-restricted diet (CR) has been shown to decrease the amount of copper bound to its carrier protein ceruloplasmin. It is the accumulation of copper over a lifetime that induces living cells in the body to become prematurely old (senescent). [Age, Aug 2012; Journal Nutritional Biochemistry Aug 2015]
With more and more adults living into their ninth and tenth decades of life, modern societies begin to wince at the prospect of a growing population of mentally demented souls. The zombification of the elderly population is worsened by over-medication. [PLoS One 2017]
It is not surprising to learn that the life-long accumulation of metals (cadmium, lead, copper, iron) is attributed to the onset of age-related dementia and memory loss. [Science Total Environment Jan 2017; Accounts Chemical Research May 2015; Cerebral Cortex Feb 2017]
Nor is it a surprise to learn that modern medicine is exploring the commercial use of synthetic mineral chelators to reverse age-related memory loss. [Neurobiology Aging Feb 2013; Journal Alzheimer’s Disease 2016] One such mineral chelator is administered nasally. [Neurobiology Aging Feb 2013] These synthetic chelators, as safe as they are reported to be, are fraught with potential side effects. [Drug Design Development Therapy Jan 2016; American Journal Hematology July 2016]
A group of natural small molecules known as polyphenols that can penetrate the blood/brain barrier, all which are mineral chelators, are ready for clinical trials to head off the upcoming epidemic of dementia as the human brain ages faster than the rest of the body. [Life Science Sept 15, 2016]
A list of natural chelators includes resveratrol (grapes/wine), quercetin (apple peel, onions), catechin (tea), IP6 phytate (bran). But these human clinical trials will take a decade to complete. By that time, it will be too late. And why allow the accumulation of metals in the brain to progress to mental decline before prescribing chelation therapy. The mass use of mineral chelating nutraceuticals is a more practical, timely and safer approach for the population at large. But will the aging masses catch on before they are so demented they can’t comprehend anything?
Does any of this work in humans or has it been demonstrated in humans yet? Well, resveratrol (150 mg/day) has recently been shown to improve the mental status and memory of women age 45-85 years who were judged to have normal mental function at the beginning of a 14-week study. [Nutrients Jan 2017]
With all of this said, the above information only applies to longevity and health seekers. For the masses they are narrowly interested in maintaining youthfulness, not necessarily living longer. Thick dark hair, smooth skin and “Viagra baby!” — that is their plea. Who wants to live longer only to look older? Consider how much money people spend to appear younger (contact lenses, skin creams, hair dyes, wigs, plastic surgery) versus live longer.
Given those demands to restore youthfulness, the following is presented:
Reading all this one would think resveratrol would be the world’s first trillion-dollar nutraceutical. The resveratrol revolution has been thwarted by many factors: fear of outliving retirement funds, lack of physician recommendation, lack of payment by health insurance, false claims of bogus research, mistaken claims resveratrol is not biologically available, covert shunning of resveratrol by physicians for fear it will lead to less doctoring, etc.
Since resveratrol first came into the public eye in 2004, sales are only estimated at ~$30 million a year for U.S. 513 brands listed on the Natural Medicine Comprehensive Database as of March 2017. There are probably less than 125,000 regular users of resveratrol in the U.S. Compare that to 50 million aspirin users or 13 million statin drug users in the U.S.
One million users of resveratrol pills @$20/30-day supply would generate $240 million in annual sales. So far, after all the ballyhoo about resveratrol, it is barely a blip in the healthcare fabric of America. That’s just where modern medicine wants it. #### ©2017 Bill Sardi, ResveratrolNews.com