• A unifying theory of aging, part 3

    January 3, 2007: by Bill Sardi

    Longevinex® is more than resveratrol

    Iron control

    The human body has an elaborate system to control iron.  Iron that is unbound, that is not attached to proteins (free iron), is the most dangerous form of iron.  Unbound iron produces the hydroxyl radical, known as the most destructive species of free radical in the body.  Indeed, oxidative injury is considered a major factor in accelerated aging.

    The majority of iron in the body is bound to the red hemoglobin pigment in red blood cells.  As long as it is bound, it poses no problem.  In a controlled fashion iron is transported to the bone marrow and dropped off for production of new red blood renewal.

    Researchers in Japan have shown that young red blood cells have far less free iron than senescent red blood cells.

    Brown melanin pigment binds to iron in the skin.  Neuromelanin binds iron in the brain.  Albumin, hemoglobin and white blood cells bind to or carry iron in the blood circulation.  The liver produces an iron storage protein (ferritin), transport protein (transferrin) and a protein that is produced during infection (lactoferrin) to limit iron availability to germs during states of infection.  Excess iron is stored in the liver.

    Excess iron deposition

    Excess iron deposition (blue areas) in the liver

    Dietary control of iron

    Molecules in the diet also augment the control of iron in the body.  What are known as polyphenols of bioflavonoids, metal-binding pigments found in the rind of citrus fruits, the skin and seeds of grapes, in berries and cherries and green tea, help to control copper and iron in the body.  Polyphenols are better at controlling copper than iron.
    Substances in fruits, grapes, berries and tea called polyphenols (flavonoids) provided in fruits, grapes, berries, wine and tea, are nature’s way of helping the body control iron and copper-induced oxidation.

    Quercetin, a strong antioxidant in onions and red apples, is also a strong iron chelator. Animal studies show that quercetin can release iron from storage in the liver of animals, and the released iron is then excreted in the feces.

    The polyphenols in tea, and to a lesser extent coffee, actually decrease the absorption of iron considerably.  For comparison, orange juice, by virtue of its acidity and vitamin C content, increases absorption of iron from foods by 85 percent. Therefore, orange juice is a beverage that should be preferred during the growing years to enhance growth via the availability of iron.  Tea, wine and whole grains are the preferred beverages to slow down aging and reduce the risk of disease after age 18 for males and with the onset of menopause in females.

    Green tea, more so than black tea, binds to copper and prevents its accumulation.  Green tea prevents DNA mutation, tumors and elevation of cholesterol via its ability to bind to metallic minerals.

    When copper is added as an oxidizing agent, the addition of red wine components to cholesterol particles in a laboratory dish inhibits the oxidation (hardening) of the cholesterol by 4-fold compared to synthetic vitamin E.
    Resveratrol, a red wine molecule, exhibits remarkable ability, at moderate dietary doses, to chelate and control copper, thus reducing oxidation (hardening) of cholesterol induced by unbound copper in the body.  Resveratrol is superior in this regard to other polyphenols (bioflavonoids).  However, resveratrol does not chelate iron.

    Red wine components do not induce deficiencies of copper or zinc.  They appear to counter negative health effects of copper after they are absorbed.

    Resveratrol, as an extract from wine skin, is a stronger inhibitor of oxidation (hardening) of cholesterol than plain red wine skin powder (no extraction).

    Resveratrol works at very low concentrations.  A grape extract diluted 8000 times was still able to inhibit the hardening of cholesterol in a laboratory study.

    The Sirtuin 1 gene is a DNA repair gene that is activated by resveratrol. DNA repair, including repair of double-strand DNA breaks, is accelerated when cells are exposed to resveratrol.

    Phytate from rice bran

    The major iron-controlling molecule in the human diet is phytic acid, found in bran, whole grains and seeds. Phytic acid-IP6 is widely known for its anti-cancer properties.

    IP6 phytate molecule

    IP6 phytate molecule
    (Inositol + 6 phosphorus molecules)

    Phytate IP6 also addresses the antioxidant theory of aging by reducing oxygen free radicals.  About 2 percent of oxygen molecules will loss an electron and become a tissue-destructive free radical.  This means an estimated 20 billion oxygen free radicals will be produced daily.  Phytate IP6 reduces oxidative damage in the body by (1) removal of iron; (2) attachment to free unbound iron; (3) removal of iron stores, such as from the liver; (4) and more uniquely, by reducing oxygen affinity to red blood cells.  If fewer oxygen molecules are being delivered to tissues, oxygen free-radical production is reduced.  Red blood cells survive longer when modified by phytate IP6.

    It is interesting to note that the Food & Drug Administration approved health claims for soy protein in 1999 as a food that reduces the risk for heart disease.  But the ingredients in soy that produce this health benefit were not identified at the time.  Subsequent studies reveal an iron-controlling molecule abundant in soy, phytate IP6, is what produces the cardiovascular health benefits in soy protein, not the widely touted weak estrogen-like molecules (phytoestrogens) in soy.

    Phytic acid is misunderstood by dieticians.   It has been mischaracterized as an anti-nutrient that impairs the absorption of iron, copper, and other essential metallic minerals, inducing anemias (shortages of iron, copper, etc).  Dieticians often recommend phytic acid be removed from foods as it impairs growth during childhood and may contribute to anemia among fertile women.  However, the need for metallic minerals is greater during childhood and by menstruating and pregnant females.  Phytic acid needs re-evaluation.  It is an important molecule in the control of iron-induced disease throughout the body.

    Phytate IP6 inhibits and reverses calcification

    The iron-chelating properties of phytate IP6 have overshadowed its ability to chelate calcium.  Phytate IP6 also has strong calcium chelating properties.  Phytate IP6 can inhibit crystallization of calcium crystals and clear calcium deposits from kidneys (kidney stones). Phytate IP6 inhibits calcifications in the cardiovascular system.

    Telomeres and IP6

    Another theory of aging is also addressed by phytate IP6.  As they age, cells begin to become shorter.  The end caps, or telomeres, on germ cells, stem cells, and most cancer cells are progressively shortened with advancing age.  The telomere theory of aging rests on the discovery that telomeres shorten each time a cell divides.  The enzyme telomerase is critical for this shortening process, which also induces immortality to cancer cells.  It has been shown that phytate IP6 represses the activation of telomerase and thus prevents cancer cells from becoming immortal.

    Telomeres

    Telomeres are end caps on
    chromosomes. The shortening of
    telomeres correlates with aging.

    Resveratrol also inhibits telomerase effectively.

    Phytate IP6 and DNA repair

    DNADNA

    Single strand DNA break (left) and double-strand DNA break (right)

    DNA damage is proposed by some biologists as the primary cause of aging. Breaks in DNA must be repaired.  For the longest time researchers could not determine how a double-strand DNA break is repaired.  Only recently has it been determined that phytate IP6 facilitates stimulation of the joining of complementary ends of DNA in double-stand DNA breaks.  This makes phytate IP6 critical for cellular repair and longevity.

    Cell

    Overmineralization and the mitochondrial theory of aging

    Mitochondrial dysfunction is considered one of the earliest changes that predict the onset of disease and premature aging.
    Overmineralization of mitochondria, the energy-producing compartments with living cells, is involved in the aging and death of mitochondria and the rate of aging in the entire body.

    Mitochondria are miniature thread-like organs within living cells.  The mitochondria produce up to 80% of cellular energy needs.  To produce energy, the mitochondria use as fuel more than 90 percent of the oxygen that a person inhales. The mitochondria are also where 95 percent of the oxidation or rusting occurs within the body.

    A brief description of the role of the mitochondria in the body is in order.  There may be 20-2500 mitochondria in each human cell in the body.  They produce the energy for muscle activity, heart pumping, breathing, brain function, etc.  More than 90% of all the oxidation that occurs in the body occurs within the mitochondria.

    Finding the biological clock:  it’s in the mitochondria

    In 1972 Denham Harman first suggested that the mitochondria might be the biological clock for the body.  Later, in 1980 J. Miquel proposed the mitochondrial theory of aging.  The production rate of “rusting agents” (iron and oxygen induced free radicals) within the mitochondria correlate with the maximal life span of any species of life.  Mitochondrial oxidation in females is significantly lower than males, which may help explain why females outlive males.

    Mitochondrial DNA

    The DNA genetic material in the mitochondria is more vulnerable to damage than DNA in the nucleus of cells.  DNA in the cell nucleus is protected by virtue of its wrapping around histone bodies (like thread around a spool).  But mitochondrial DNA has no such protection.  Oxidative damage to DNA in the mitochondria is many times greater than DNA in the cell nucleus.  By age 90 only about 5% of the mitochondrial DNA is intact in a male.

    Researchers at the Karolinska Institute in Stockholm, Sweden, report that mutations in mitochondrial DNA have a causal relationship with aging in mammals.  When mice are engineered to carry a damaged version of a mitochondrial enzyme, damage in the mitochondria increases 3-fold and by 25 weeks of age, which is young adulthood for rodents, the mutations begin to emanate into visible signs of aging — baldness, heart problems, bone thinning and reduced fertility.  None of the animals lived beyond 60 weeks when healthy mice live 100 weeks on average.

    It’s amazing that these small cell bodies exert so much control over aging.  Mitochondria die off or exhibit mutation rates in a programmed fashion, accelerated by production of oxygen free-radicals.  By slowing down or even switching this programmed death off, it’s possible aging itself can be slowed.

    What causes all this trouble in the mitochondria with advancing age? — the accumulation of iron and calcium.  Iron deposition in the mitochondria is a unifying theory of aging. The major free radical produced within the mitochondria is the superoxide radical, which releases iron from binding proteins.

    mitochondria

    The chelation (removal) of iron and calcium has been proposed as an anti-aging strategy in the mitochondria.

    Lipofuscin, an aging pigment that impairs cellular function, can form within the mitochondria due to the iron-induced oxidation of cellular debris.  Chelation of iron would reverse or stop lipofuscin formation.

    CONTINUE TO PART 4

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