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  • Resveratrol Works Indirectly Via Its Ability To Beneficially Alter Gut Bacteria, But Does That Result In Superlongevity Or Just Super-Health?

    April 24, 2016: by Bill Sardi

    It has been recognized for over a decade that red wine molecules known as polyphenols favorably alter the makeup of gut bacteria to reduce risk for colon cancer and inhibit growth of implanted tumor cells. [Mutation Research 2005] But until a recently reported study strikingly demonstrated how resveratrol inhibits accumulation of fatty plaques in the walls of arteries via its ability to alter the composition of bacteria in the intestines, this indirect mechanism has been largely overlooked. [MBio April 5, 2016]

    The ability of red wine molecules to foster the growth of healthy bacteria in the intestines, namely Bifidus, is now well established. [Redox Biology 2014; Food & Function 2016; Journal Clinical Gastroenterology 2012]

    To quickly summarize, this means gut bacteria control life-threatening diseases such as cancer and coronary artery disease and should have a dramatic effect over the leading causes of death (mortality), not just chronic non-life threatening disease (morbidity). Said another way, resveratrol is not limited to promotion of intestinal health via its direct contact with tissues in the digestive tract. [Redox Biology 2014]

    Even more intriguing, resveratrol by virtue of its ability to alter gut bacteria elevates mood. This means resveratrol indirectly alters biological activity in a remote organ that is protected by a blood-brain barrier. [] Gut bacteria influences dopamine secretion, a brain chemical required for working memory, learning and movement. [Psychoneuroendocrinology 2014] The age-related decline in dopamine secretion, said to decline at the rate of 13% for every decade of life after age 45. [Acta Neurologica Scandinavia 1983]

    On this basis, dopamine secretion would decline to around 30% of normal by age 130 years, which is the level where Parkinson’s disease occurs. Given that death does not occur for some other reasons, declining dopamine secretion would continue with advancing age to 10% when would inevitably induce death. [CNS Drug Review 2001] Resveratrol protects dopamine-producing cells in the brain. [ European Journal Pharmacology 2008]

    As remarkable as these discoveries are, a larger questions remains: while resveratrol and other accompanying polyphenols may have pervasive effects over morbidity and mortality in humans via gut bacteria, does this translate into longevity? Currently published literature suggests resveratrol specifically and polyphenols in general may indeed live up to their advertised claim as anti-aging agents.

    Progressive aging is known to demonstrably alter the composition of gut bacteria in humans. Changes in gut bacteria in senior adults are linked to chronic low-grade inflammation and a compromised immune system (called inflammaging and immunosenescence). Long-lived centenarians exhibit a different pattern of gut bacteria and are able to produce molecules such as butyrate and acetate (short-chain fatty acids) that are a source of energy for the lining of the gastrointestinal tract, are involved in the production of mucin and maintenance of immunity. [Aging 2013]

    Could gut bacteria be the missing element in centenarians that confers superlongevity, where the phenotype (interaction of genes and the environment) predominates over the human genotype (inherited arrangement of intact genes)? (PLoS One 2013] Certainly, “an important role of the gut bacteria in aging and longevity is emerging,” say anti-aging researchers. [Biogerontology 2011]

    If true, that gut bacteria control aging, at least to some significant degree, then the universally accepted calorie-restricted diet that doubles the lifespan and healthspan of laboratory animals, should be shown to favorably alter gut bacteria. Indeed, calorie restriction improves human metabolism (burning of calories, control of blood sugar) via altered composition of gut bacteria. [Gut 2016; CNS Neurological Disorders Drug Targets 2014; Nature Communications 2013]

    If you can imagine this, Greek-born Australians who adhere to a Mediterranean Diet were compared to Anglo-Australians. Even though Anglo-Australians were less obese (only 10%) than their Greek-born Australians (30-46% obese), and despite the fact Greek-born Australians consumed more red meat, cheese, milk, butter, margarine, white bread and sugar, Greek-born Australians exhibited a 35% lower mortality rate from cancer and cardiovascular disease! [Asia Pacific Journal Clinical Nutrition 2014]

    A varied plant food diet that favorably influenced the gut bacteria is attributed to this striking paradox. The consumption of legumes (peas, beans, lentils, carob, nuts) along with polyphenols from grapes, wine and olive oil, were noted as dietary factors involved in this paradox. In other words, polyphenols along with other dietary components virtually erased the effects of an imprudent fat-laden diet.

    These findings have led to a challenge to the energy-in/energy/out model of weight control. Some foods (such as fructose and purine-rich foods such as meat and seafood) that stimulate uric acid encourage fat accumulation whereas other foods (such as fermented soy/ miso and tempeh and other legumes, polyphenols and omega-3 oil from flaxseed and fish) counteract the negative effects of a calorie-rich diet. Researchers write: “Overeating and overshooting of calories could to a large extent represent a symptom rather than a cause of obesity.” [Nephrology Dialysis Transplantation 2015]

    Inflammation-limiting gut bacteria predominate in long living human populations. [BMC Microbiology 2015] More specifically, high-fiber diets that favorably alter gut bacteria are associated with achieving long life. [Journal Microbiology Biotechnology 2015]

    However, it should be noted that not all fiber is prebiotic, that is, promotes growth of healthy bacteria (namely Bifidus) in the human intestines. Foods such as asparagus, chicory, artichokes, onions, garlic, oats are prebiotic. [Nutrients 2013] Consumption of these prebiotics with fats (such as steamed artichoke with butter) negates some of the beneficial effects of probiotics. [Bioscience Microbiota Food & Health 2013]

    The mechanisms may vary from prebiotic to prebiotic. For example, garlic is known as a natural antibiotic and prebiotic. Does garlic kill off beneficial and pathogenic bacteria? Studies reveal garlic selectively kills off troublesome bacteria by virtue of acid-forming bacteria being more resistant to garlic’s germ-killing properties. [Phytomedicine 2012]

    The discovery that polyphenols, largely provided in beverages such as wine, coffee and tea, are prebiotic, also add to the growing knowledge base how longevity is achieved. [Current Obesity Reports 2015; Journal Agriculture Food Chemistry 2013]

    It should not be presumed that all polyphenols encourage the growth of the same beneficial gut bacteria to the same degree. Distinct differences in gut bacterial composition between polyphenols in tea and wine have been noted. [Journal Agriculture Food Chemistry 2010]

    Whereas well-known prebiotics (defined as agents that promote the growth of beneficial gut bacteria versus probiotics that like Lactobacillus acidophilus and Bifidus which are microbes themselves) like inulin from chicory or fructooligosaccharides (pronunciation: fruck-toe-oli-go-sack-a-rides) from asparagus, onions, Jerusalem artichoke and garlic, favor the growth of some healthy gut bacteria (Bifidus, Bacteroides) along with some unhealthy bacteria (Clostridium). Distinctively, polyphenols suppress Bacteroides and Clostridium but enhance the growth of Bifidus. [Bioscience Microbiota Food & Health 2013] Therefore, there is increased scientific interest in polyphenolic-based prebiotics.

    While there is continued scientific and lay person fascination with genetics, the structure (genetics) and dynamic nutritionally-controlled protein-making of genes (epigenetics) do not fully explain human aging. Aging researchers say (paraphrased): “the identification of longevity-related genes does not explain the mechanisms of healthy aging and longevity and poses questions on the contribution of the gene regulation… To fully disentangle what appears to be an endless quest, all the components of human longevity genetics need to be taken into account.” [Current Vascular Pharmacology 2014]

    Anti-aging researchers write about thyroid hormone deficient Dwarf mice that live up to 50% longer than common laboratory mice the same mice that decades earlier were used as a model to study progeria, an accelerated human aging syndrome where youngsters exhibit cataracts, wrinkled skin and other signs of aging early in life. This strongly suggests the nutritional environment can alter what was once thought to be inevitable genetically. The mice were not different, their environment was. “A once progeric mouse became a long-lived hope” is how researchers described it.

    These same researchers say rather than altering single aging genes (like Sirtuin1) “we might be targeting the wrong genome (the human genome rather than the library of genes in our gut bacteria referred to as the microbiome)… we should pay equal attention to prebiotic regulation of longevity as an alternate means to the same end.” [Cell 2014] — ©2016 Bill Sardi,

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