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How the world got lost on
the road to an anti-aging pill
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December 18, 2017: by Bill Sardi
It could be said that the “aging is optional” era began ~2003-2004 when geneticist David Sinclair of Harvard Medical School announced a connection between a life-doubling calorie restricted diet, the Sirtuin1 survival gene and the red wine molecule resveratrol (rez-vare-ah-trol).
Actually a decade earlier (1992) two researchers at Cornell University posited that resveratrol may be the active ingredient in wine that lowers circulating levels of cholesterol.
In the 1990s the French were drinking 3-5 glasses of aged red wine and not paying a price for it. The French had higher cholesterol levels but a coronary artery death rate of ~90 per 100,000 versus 240 per 100,000 in North America. Today the mortality rate for heart disease is 168.5 per 100,000 in the U.S. and is as low as 116.6 in Minnesota and 128.4 in Colorado and as high as 240.5 in Mississippi and 223.2 in Arkansas.
A large decrease in coronary heart disease, about 20%, reported in the US between the years 1983-2011 goes unexplained. Modern cardiology takes credit for this drop but it couldn’t possibly be due to better treatment. Statin drugs lower circulating cholesterol levels but only slightly reduce the rate of non-mortal heart attacks.
A careful analysis of factors that could be attributed to this decline in coronary heart disease mortality identified increased wine consumption as the likely explanation.
Imagine if this came to be widely known instead of the prevailing false notion, promulgated further by what now appears to be corporately controlled news media, that modern medicine and its myriads of problematic drugs and surgical treatments are responsible for this decline in mortality.
Yes, giving license to wine drinking would spawn a generation of alcoholics with liver problems, but for those who would drink in moderation, they would be counter the modern sin of overeating just as the French do now. And let’s not forget that the French drink dark aged, mostly red wine which is rich in polyphenols that Dr. Roger Corder of William Harvey Research Institute in London and author The Wine Diet says is the reason why wine is attributed to produce unusual longevity.
There are presently 21,000 centenarians in France out of a population of 67 million (~3 in 10,000). By 2070 it is projected there will be 270,000 centenarians living in France with an anticipated population of 76 million (or 3.5 per 1000!).
Compare France to the U.S. (2014) where there are an estimated 72,197 centenarians out of a population of 325 million (or about 2.0 in 10,000). The wine drinking French have more than 1.75-fold more centenarians than the U.S.
In the pursuit of longevity, given there are innovators, early-adaptors, late-adaptors and finally laggards, historically a couple of individuals were way ahead on the curve.
The longest living human in modern times, Jean Calment of France (1875-1997), drank a glass of port wine and a bit of chocolate daily. Both contained polyphenolic molecules. Calment lived 122 robust years.
Historically, the written record of Luigi Cornaro, who lived in Padua, Italy from 1454 to 1566 AD, was advised in his 30s that he was a glutton and a drunkard by his physicians. From that point forward Cornaro adopted a limited calorie diet (12 ounces a day) and trimmed his wine consumption to 14 ounces. Only an Italian would think 3 glasses of wine a day as a cutback. Cornaro lived 102 healthy years practicing what today would be a called a calorie restricted diet + a resveratrol pill. (Wine then was unfiltered and provided 30 times more polyphenolic molecules as today’s filtered wines.)
Those early adaptors who chose to take a cheap synthetic untested resveratrol pill may have fooled themselves.
The lesson from Mr. Cornaro is that it is possible for anyone to get ahead of the adoption curve. Those innovators who dared to take a resveratrol pill ventured ahead of the rest of society.
However, those individuals who chose to take a cheap synthetic untested resveratrol pill may have fooled themselves. A leading group of anti-aging scientists recently reported synthetic resveratrol does not exhibit epigenetic activity; only a molecular combination of molecules including resveratrol extracted from a botanical source (Longevinex®) does.
But something greater was achieved on September 11, 2003 when Dr. Sinclair announced his compelling study showing yeast cells lived far longer when given resveratrol. Up to that point in time, biology had been hiding a secret.
It had been observed in the 1970s there was something other than genetic inheritance that was influencing human health and longevity. Japanese people migrating to Hawaii experienced changes in their health and lifespan. Something other than the fatalist concept that you either inherit longevity from your ancestors or you don’t.
Jean Calment, the oldest living human in modern times, who died at age 122 was found to have a very high ancestral longevity score. But was her superlongevity due to the sequence of the nucleotides on her DNA ladder, in other words, inherited, or was it something more dynamic?
That dynamic factor was identified as epigenetics, the discovery that environmental factors (diet, solar radiation, temperature) activate (express) or de-activate (silence) genes, and whatever gene expression that was going on in the womb or early after birth produced epigenetic imprinting that could be passed on to succeeding generations.
It is striking to learn how much science goes ignored for so long. Way back in 1958 researcher D. L. Nanney described the “existence of differences between cells with the same inheritance that are not entirely determined by DNA (paraphrased).” The whole era of epigenetics could have been swept into existence 50 years earlier.
Then in 1998 researchers affiliated with the National Center for Toxicological Research in Arkansas reported that the provision of a dietary supplement to a special breed of pregnant mice during pregnancy affected the longevity of these animals.
Not only does food, or the lack of it as evidenced in calorie-restricted longevity diets, influence our genes but also those of succeeding generations. As Dr. Randy Jirtle writes, a long-standing assumption in biology was that gene mutations (interruptions in the sequence of DNA) were the exclusive source of inherited characteristics including longevity. Dr. Jirtle presents examples of non-DNA sequence-based inheritance that traverse across generations as demonstrated in plants, worms, flies, fish, rodents and humans.
Dr. Jirtle points to studies that show limited intake of food due to foodstuff shortages and famines during a father’s slow growth period when he was 9-12 years of age confer lower risk for cardiovascular disease mortality in his offspring whereas an overeating pattern during the same stage of development results in up to a fourfold increase in diabetes mortality in their grandchildren. Just precisely how much epigenetics contributes to inherited longevity is still yet to be fully determined.
From the year 2004 forward mankind could pretend to mount a concerted effort to re-produce superlongevity achieved in the animal laboratory, a doubling of the healthspan and lifespan, or even an indefinitely long life expectancy.
Skeptics and naysayers demanded conclusive evidence. That would mean a life-long study of adults, half taking a resveratrol pill and half taking an inactive placebo pill. Of course, such a study would cost hundreds of millions of dollars and would be impractical.
A decade and a half later since a Harvard professor first gained worldwide attention for a resveratrol pill, the idea is yet to be conclusively proven. And almost before the whole idea gained any traction, it is being dismissed.
In a report entitled “Evidence for a limit to human lifespan,” investigators mathematically concluded that human lifespan is limited to 115 years and the probability of a lifetime exceeding 125 in any given year is less than 1 in 10,000.”
Without any real longevity trials of resveratrol pills in humans, the prospects of a long and healthy life were temporarily dashed, but not for long. Five different papers were rapidly published in rebuttal.
The limiting factor in lifespan extension is the progressive accumulation of molecular damage inside cells. Endogenous repair mechanisms are in place but are overwhelmed over time. However, in animal experiments DNA damage diminishes when levels of NAD are increased. Resveratrol increases NAD (nicotinamide adenine dinucleotide which is adenine + nicotinamide, a derivation of niacin/vitamin B3), which converts to NADH. Resveratrol elevates NAD levels better than niacin derivatives.
Now some biologists say an increase in human life expectancy to over 125 years “appears to be reasonable.”
According to another recent report, errors in DNA repair can result in accumulation of DNA damage product, which results in premature aging. Agents like resveratrol and fish oil that can help maintain epigenetic stability and facilitate DNA repair “can slow down the progress of premature aging, if not completely prevent it.”
Other biologists say, upon examination of other pathways and interventions, all which significantly extended the median, maximum and last survivor lifespans not considered in prior reviews, forces the conclusion that “biologic genetic causes of aging can allow breaking the currently observed ceiling of human maximum lifespan.”
A recent comparison of adults, age 34-103 years, found those individuals who had achieved exceptional longevity have a young epigenetic age compared with their chronological (calendar) age.
But while scientific advancements are being published almost daily, the political climate for anti-aging pills soured. The Department of Justice is now legally emboldened to prosecute any company that makes anti-aging claims for its products. Enforcement has been delegated to bankers who arbitrarily cancel online merchant accounts if they find anti-aging claims being made in online advertising. Only billionaire oligarchs are now allowed to make such claims.
Modern humans are being fed processed foods like lab rats in a laboratory experiment. So the more imminent question is whether there is an antidote to the global diabesity epidemic that began with the use of high-fructose corn syrup, largely in soda pop? Would such a pill give license to over-eat? That question was first asked in a 2007 report entitled: “If You Have Your Wine, Can You Eat Your Cake Too?”
Since 2004 it has been learned that the broadly published Food Pyramid, fashioned largely by commercial forces that promoted sugars and carbohydrates over dietary fats, had led humanity in the wrong direction. The high-fructose generation would produce more disease for the medical industry to treat and concomitant drugs to prescribe for Big Pharma.
In Nina Teichholz’s book The Big Fat Surprise we learn that refined sugar and carbohydrates (cereal, pasta, bread) that turn to sugar are the real metabolic demons, not fat. The sugar industry hid evidence that table sugar (sucrose) consumption raises blood cholesterol levels and elevates the risk for coronary heart disease. Believe it or not, butter and lard are back on the table. When America wasn’t so fat phobic, Americans were lean. The proposed answer was more physical exercise, but even then, resveratrol pills were proposed as exercise mimetics.
As long as demand for resveratrol pills remains low and creates little competition for Big Pharma, and doesn’t reduce levels of disease that corporate medicine relies upon to produce profits and maintain stock values, the public will have access to this molecule that is “many drugs in one.” But if you begin to read positive news reports about resveratrol, anticipate more researchers will be falsely accused of fraud and negative news reports will follow. Fake news is not just political.
This author recalls the knee-jerk response from Harvard Medical School when my book The Anti-Aging Pill was published in 2004. A Harvard professor came forward on a television interview to say it was the alcohol in red wine, not resveratrol, that produces a cholesterol-lowering effect. Harvard wasn’t going to tolerate any groundswell in demand for resveratrol pills unless it has their imprimatur on it.
For those who decided long ago to include a resveratrol pill in their daily supplement regimen, most acted on faith that subsequent science would validate the promise posed by red wine pills. For the most part, that has been validated, but not for every resveratrol pill among the 530 brands commercially available.
Jumping in an elevator requires faith it will lift people safely to the 64th floor of a tall building. But I wonder how many people would opt to take the stairs if they began hearing contrived reports about people dying from elevator failures? Some die-hard resveratrol pill users wouldn’t cease taking their pills, but there are many who can be easily swayed by fear to abandon their use. Should public demand for resveratrol pills rise significantly, anticipate negative publicity will suddenly and inexplicably follow.
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