• A unifying theory of aging, part 4

    January 3, 2007: by Bill Sardi

    Longevinex® is more than resveratrol

    Another theory of aging: cell cleansing

    Another overlapping theory of aging is the “cell cleansing” theory.  Living cells must rid themselves of debris.  Cell bodies called lysosomes literally digest and recycle cellular debris, a process that even provides a source of cellular energy (food) in the event of starvation.

    This cellular cleansing process is called autophagy.  Activation of autophagy can increase longevity. With advancing age, the garbage-digesting lysosomes and the energy-producing mitochondria in living cells eventually become burdened with excessive iron and calcium as well as other metallic minerals.  Aged lysomes progressively fail to perform cell cleansing chores and the cell dies.

    The failure of the lysosomes to continually cleanse cells of debris is now considered a form of programmed cell death.

    The failure of cells to cleanse themselves of debris is also associated with the occurrence of tumors.

    Both lysosomes and mitochondria are vulnerable to oxidative stress induced by iron.

    Calorie restriction is known to activate autophagy (cell cleansing). Near starvation of animals increases autophagy and longevity.

    The use of iron chelators has also been shown to reverse the accumulation of cellular debris within aged cells, in a similar manner to calorie restriction.

    Iron chelation also reverses the progressive rupture of lysosomes and prolongs the life of cells.

    It is interesting to note that resveratrol activates autophagy (cell cleansing), which can either prolong the life of healthy cells, or shorten the life of tumor cells. Phyate IP6, being an iron chelator, would also be anticipated to increase cell cleansing via autophagy.

    lysosome

    Graphic showing a lysosome that has enzymatically
    “digested” two damaged parts of a living cell
    (damaged mitochondria and peroxisome).

    lysosomes

    Botanicals and the mitochondria

    Natural molecules can play a strong role in protecting the mitochondria from oxidative damage.

    For example, the DNA damage caused within the mitochondria is primarily caused by the superoxide radical. Resveratrol inhibits the formation of the superoxide radical.

    Resveratrol has been shown to oppose the production of free radicals that cause mutations in the mitochondria. Furthermore, resveratrol works in multiple ways to preserve mitochondria from damage.

    Phytate IP6 has also been shown to regulate the influx of calcium into mitochondria, thus protecting mitochondria from oxidative damage.

    Resveratrol and iron

    While resveratrol is not a direct iron chelator, it does exert control over iron in living tissues via the production of an enzyme called heme oxygenase.  Mice bred so they cannot produce heme oxygenase accumulate dangerous levels of iron in different organs.  Resveratrol activates heme oxygenase activity, which controls iron and therefore prevents damage and aging in living tissues.

    The miracle of resveratrol is that it activates production of heme oxygenase in the brain and heart before events such as strokes and heart attacks occur.  Otherwise, heme oxygenase is upregulated only after such events.  This is a remarkable “pre-conditioning effect” that serves to prevent damage to brain and heart tissues.

    Final corroboration: why aging ceases late in life

    As final corroboration of the overmineralization theory of aging, an astounding and unexpected discovery was announced in 1992 – that aging ceases in late life.  There is a flattening of the death rate late in adult life in many species (insects, worms, yeasts) and humans.  At the greatest ages, mortality rates actually may decline. , , ,

    Lame attempts have been made to explain why aging ceases in the very old.

    No one made much of this discovery, announced in 1992 and it has remained an inexplicable phenomenon, till now.
    “The discovery that aging ceases is one the most significant discoveries in recent aging research, with potentially revolutionary implications,” says Michael R. Rose and colleagues at the Department of Ecology and Evolutionary Biology, University of California, Irvine.

    This discovery casts doubt on the idea that species have absolute life-span limits.

    The cessation of aging in advanced stages of life can be correlated with the cessation of iron accumulation in the very old.  Males accumulate iron till middle age.  Females only begin to accumulate iron with cessation of menstruation (menopause or early hysterectomy).

    A 10-year study of adults who ranged in age from 60-93 years shows that iron storage levels (as measured by ferritin, a protein made in the liver that carries iron), level off and do not continue to rise in this age group.  This is called “achieving a steady state level” of iron, that is, iron absorption is thought to be limited to amounts required to match that necessary to replace losses. The age at which an individual achieves his or her theoretical setpoint of iron stores has not been determined.

    Dietary iron intake up to 10 milligrams achieves iron adequacy without inducing anemia.  Iron supplements providing 18 milligrams of iron continue to add to the iron load of an individual at this age.

    The drawback of the above human study was that ferritin, the storage protein for iron, is often elevated in humans from chronic infection, inflammation or disease, which can result in misleading numbers.  So researchers at Pennsylvania State University sought to validate the idea that iron reaches a steady state of storage in advanced age by conducting a controlled animal experiment.  They found that old rats had significantly lower hemoglobin and blood plasma iron levels than middle-age rats, and lower total iron content in liver, spleen and bone marrow.

    Iron-Related Blood Measures Decline in Old Age
    Age of rats Hemoglobin, g/L Plasma iron, µmol/L
    Middle-aged rats 186.1 42.9
    Old rats 147.8 23.2
    Iron Content of Various Tissues of Old and Middle-Age Rats
    µmol = micromolar concentration
    Rat Age Liver iron Spleen iron Femur marrow iron
    conc
    µmol
    µmol/gram
    wet tissue
    conc
    µmol
    µmol/gram
    wet tissue
    conc
    µmol
    µmol/gram
    wet tissue
    Middle-aged 57.59 2.98 11.23 13.53 0.11 2.90
    Old 23.36 1.40 7.35 4.56 0.07 1.20

    Summary and conclusions

    The overmineralization theory of aging helps to explain, and appears to be a predominant if not controlling factor, over the hormonal, oxidation and mitochondrial theories of aging.  Overmineralization also is involved in the decline in melatonin production with advancing age.   The pineal gland that secretes melatonin is considered the body’s biological synchronizing clock.

    Iron has been called the “malignant spirit of successful aging.” Iron deprivation has been proposed as an anti-aging strategy. Barbara S. Polla, a researcher with the Latoratoire de Physiologie Respiratoire in Paris, France says that “moderate iron deprivation might shortly add to other anti-aging ‘miracles’” and that iron chelators may “shortly become the most efficient and fashionable antioxidant, anti-aging, anti-infectious, and anti-inflammatory therapy.”
    Iron control appears to prolong or shorten the lifespan of many life forms.  It is interesting to note that a gene that regulates senescence in wheat grain controls the iron and zinc content of the grain.

    Calorie restriction and molecular mimetics

    Calorie restriction and its molecular mimic resveratrol have received much attention recently as anti-aging strategies.  Calorie restriction is considered an unequivocal approach to prolonging life in all organisms.  Seventy years of study confirms that calorie restriction decreases the rate of aging by lowering the generation of free radicals in the mitochondria of cells.

    The key experiment, presented earlier in this paper, conducted by researchers at McGill University in Canada, conclusively showed that dietary restriction did NOT reduce the number of aging deposits in brain tissues compared to rats fed a normal diet, but did reduce aging deposits in the brain when a standard calorie-restricted diet with low metallic mineral content was compared against a diet where animals ate a restricted-calorie diet with added metallic minerals.51  It’s the minerals, not the calories, that control aging.

    Luigi Cornaro

    Luigi Cornaro (1464-1566 AD), of Padua, Italy,
    preceded recent discoveries that calorie
    restriction and red wine resveratrol
    can prolong human life, by limiting intake
    of food to 12 ounces, and red wine to
    3 glasses per day,and lived 102 years
    in excellent health to his dying day.

    From a gene-switching standpoint, calorie restriction activates the Sirtuin 1 gene, which increases the life span of many organisms.

    When the question arose, could the Sirtuin 1 gene, activated by calorie restriction, also be activated molecularly without food deprivation, researchers were quick to answer the question. Resveratrol, a red wine molecule, has now been identified as a molecular mimic of calorie restriction and activator of the Sirtuin 1 DNA repair gene.

    The health benefits of calorie restriction mimics are not new.  The French, by virtue of their traditional consumption of red wine, have been activating the Sirtuin 1 gene for some time.  The French live 45-65% longer in wine-growing districts.

    There is even the meticulously documented presentation of a man, Luigi Cornaro, who lived in Padua, Italy over 500 years ago, who limited his food intake to 12 ounces, and wine intake to 3 glasses per day, and lived 102 years.

    Even though the French utilize a dietary source of resveratrol and benefit with leaner bodies and lower cardiovascular mortality rates from the traditional consumption of red wine, the drawback of alcohol and calories in wine can be overcome with a red wine pill.  So we now live in an era of calorie restriction mimics.

    Resveratrol, the molecular mimic of calorie restriction, appears ready to make its impact upon human health as a dietary supplement.  While resveratrol will continue to captivate scientists and the public, it is not the only life-prolonging molecule nature provides.

    Recent discoveries involving gene switching with small molecules like resveratrol should not overshadow the overmineralization theory of aging and the advantage of a broader array of mineral chelators, such as phytate IP6 and quercetin, to waylay aging.  (Subject of an applied-for patent.)

    Other recent efforts have already been made to unify the many theories of aging. This paper broadens the understanding of life extension even more.

    Longevinex® provides a unique array of mineral chelating ingredients, resveratrol, quercetin and phytate IP6, that address the accumulation of iron, copper, calcium and other heavy metals in the human body with advancing age.

    MINERAL CHELATORS IN LONGEVINEX®
    INGREDIENT CHELATES (binds to) NATURAL SOURCE
    Resveratrol* Copper Red wine grapes,
    Giant knotweed
    Phytate (IP6) bran factor Iron, copper, calcium, heavy metals Rice bran
    Quercetin Iron Onions
    * Resveratrol exerts control over iron by activation of an iron-controlling enzyme called heme oxygenase

    Copyright Bill Sardi, January 3, 2007

    Table

    Molecules 2 - table

    REFERENCES

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