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Life Extension Magazine

LE Magazine December 1995

Evidence That Melatonin Is An Anti-Aging Therapy

Recently, there's been an explosion of research studies on melatonin, which have generated an enormous amount of evidence in support of Dr. Rosenzweig's theory that melatonin plays a critical role in aging. The findings of these studies have uncovered several potential mechanisms of action to explain how melatonin affects aging and the diseases of aging.

LEF graphic The first and most basic piece of evidence that implicates melatonin in aging is that the production of melatonin by the pineal gland falls drastically with advancing age. The startling age-related decline in melatonin levels in humans has been shown by scientists such as N.P.V. Nair of McGill University in Montreal and Russel J. Reiter of the University of Texas Health Science Center in San Antonio.

The data indicate that peak nighttime levels of melatonin in humans are about twice as high in young people (21-25 years) than in middle aged people (51-55 years), and about four times as high in young people than in old people (82-86 years). The 24-hour secretion of plasma melatonin has been shown to be approximately twice as high in 20-year-old men and women as in 60-year-old men and women.

These findings suggest that the age-related depletion of melatonin may be a cause of the deficits and diseases associated with aging.

The Super Antioxidant

Dr. Denham Harman of the University of Nebraska in Omaha is the originator of the free radical theory of aging. Free radicals are molecules containing an unpaired electron in their outermost orbital ring, which makes them extremely reactive and short-lived. The interaction of oxygen and other chemicals is the primary source of free radicals within our bodies. In the past 50 years, there has been a huge, rapidly growing body of evidence linking uncontrolled free radical activity to aging and the degenerative diseases of aging.

Over the years, free radical scientists have identified a number of substances (called antioxidants) that counteract the damaging effects of excessive free radical activity. Among these are the enzymes super oxide dismutase, glutathione peroxidase, and catalase, and compounds such as vitamin E, vitamin C, selenium, glutathione, cysteine and methionine, and uric acid. Scientists have also found antioxidant properties in drugs such as deprenyl, hydergine, and centrophenoxine.

A Better Hydroxyl Scavenger Than Glutathione

The knowledge that melatonin is one of the body's own natural antioxidants is of very recent vintage. It was first proposed in 1990 and experimental evidence of melatonin's antioxidant powers has only emerged since that time.

One series of experiments showing that melatonin is a highly potent antioxidant was conducted in Dr. Reiter's lab. In one study, the carcinogen, safrole, was administered to rats, either alone or in combination with melatonin. Safrole causes nucleic acid damage in DNA via the production of oxygen radicals.

The result of the study was that melatonin almost totally knocked out the DNA-damaging effect of safrole. The amount of DNA damaged by safrole (300 mg/kg) was reduced by 41% even when the dose of safrole administered was 1,500 times greater than the dose of melatonin (0.2 mg/kg). When the dose of melatonin (0.4 mg/kg) was doubled (but stilt 750 times less than that of safrole), DNA damage was reduced by 99%!

In an in vitro study, melatonin "very significantly" reduced highly reactive Hydroxyl (.OH) radicals generated by ionizing radiation.

In another in vitro study, melatonin's ability as a free radical scavenger was compared to mannitol and glutathione, the most effective Hydroxyl radical scavengers tested to that point. The concentrations of melatonin, glutathione, and mannitol required to reduce Hydroxyl radical activity by 50% were, 21, 123, and 238 microns/M respectively. Thus, melatonin was shown to be 5.9 times more effective than glutathione and 11.3 times more effective than mannitol in fighting Hydroxyl radicals!

The Dangerous Hydroxyl Radical