The "Melatonin - DHEA Cycle" and Calorie Restriction
Copyright ã 1997, 1998 by James Michael Howard.
(This was posted to various internet newsgroups, November 10, 1998.)
I have written about the connection of melatonin and DHEA in the past. In fact, I have developed what I call the "melatonin - DHEA cycle." It is my hypothesis that melatonin and DHEA are directly involved in controlling the other, hence, the melatonin - DHEA cycle. In my explanation of sleep, you will find that when one is low, the other is high. Anyway, a short time back I posted an article here entitled "DHEA and Calorie Restriction," which was intended to demonstrate that calorie restriction works because calorie restriction reduces the daily production of DHEA, and, therefore, extends the life-span production of DHEA. Extending the availability of DHEA extends its use for an organism, hence, extending the life-span of the organism.
The following citation has just come to hand: "The production of melatonin declines with increasing age, and circulating melatonin levels are affected by certain pharmacological or physiological manipulations, notably food restriction which increases melatonin levels and prevents its age-related decline." (Gerontol 1996; 42: 87). This effect of calorie restriction on melatonin production is supported by Acta Endocrinol (Copenh) 1987; 115: 507, J Endocrinol Invest 1989; 12: 103, and Brain Res 1991; 545: 66. So, this produces a mechanism involving melatonin and DHEA which directly explains the extension in life-span produced by calorie restriction. That is, food restriction increases melatonin which inhibits the production of DHEA. Reducing the production of DHEA extends the usable life-span of production of DHEA by the adrenals. Hence, the mechanism of life-extension due to calorie extension results from an increase in melatonin, which reduces the daily production of DHEA. Hence, the production of DHEA is extended.
Here is my original post, October 24, 1998:
"DHEA and Calorie Restriction"
Since I developed my hypothesis that every cell utilizes DHEA for optimal function, I have thought that DHEA is also necessary for optimal function of all tissues. I think DHEA optimizes transcription and duplication of DNA. With that in mind, I decided that loss of DHEA results in reduced transcription and duplication of DNA. Therefore, I define aging as loss of transcription and duplication of DNA, as a result of the natural loss of DHEA. Therefore, anything that reduces the loss of DHEA, or use thereof, will extend the lifetime of DHEA and, therefore, reduce aging. Now, since fasting reduces DHEA production, eating should cause its increased use. In the following citation, which directly connects calorie restriction and DHEA, it is shown that calorie restriction reduces DHEA the "postmaturational decline in serum DHEAS levels." Therefore, it could be that the life-extending qualities of calorie restriction may actually result from an extension of the production of DHEA.
J Clin Endocrinol 1997; 82: 2093.
"Dehydroepiandrosterone sulfate: a
biomarker of primate aging slowed by calorie restriction"
Lane MA, Ingram DK, Ball SS, Roth GS
"The adrenal steroids, dehydroepiandrosterone (DHEA) and its sulfate (DHEAS), have attracted attention for their possible antiaging effects. DHEAS levels in humans decline markedly with age, suggesting the potential importance of this parameter as a biomarker of aging. Here we report that, as seen in humans, male and female rhesus monkeys exhibit a steady, age-related decline in serum DHEAS. This decline meets several criteria for a biomarker of aging, including cross-sectional and longitudinal linear decreases with age and significant stability of individual differences over time. In addition, the proportional age-related loss of DHEAS in rhesus monkeys is over twice the rate of decline observed in humans. Most important is the finding that, in rhesus monkeys, calorie restriction, which extends life span and retards aging in laboratory rodents, slows the postmaturational decline in serum DHEAS levels. This represents the first evidence that this nutritional intervention has the potential to alter aspects of postmaturational aging in a long-lived species."