Dehydroepiandrosterone, Sleep, and DNA Methylation

Copyright, July 5, 2015, James Michael Howard, Fayetteville, Arkansas, U.S.A.

I suggest DNA methylation (DNAmation) is part of an evolutionary selection mechanism of dehydroepiandrosterone (DHEA) involved in sleep.  I think DNAmation occurs as a result of low DHEA during sleep.

It is my hypothesis that evolution selected dehydroepiandrosterone (DHEA) because it optimizes replication and transcription of DNA, that is, genes.  Therefore, DHEA levels affect all tissues and all tissues compete for available DHEA, especially the brain.  (I think evolutionary selection of DHEA produced mammalia.  “Hormones in Mammalian Evolution,” Rivista di Biologia / Biology Forum 2001; 94: 177-184).  DHEA naturally begins to decline around the ages of twenty to twenty-five, reaching very low levels in old age.  When DHEA is low or decreasing, all tissues are adversely affected.

Very briefly, it is my hypothesis that the function of sleep is to produce DHEA which stimulates consciousness ( ).  My mechanism suggests that the light-dark cycle is involved in stimulating DHEA.  This requires melatonin production during the dark phase which then results in the production of DHEA. The function of sleep / circadian rhythm is production of DHEA.  This mechanism eventually produced mammalian evolution.  “Hormones in Mammalian Evolution,” Rivista di Biologia / Biology Forum 2001; 94: 177-184.  If your library does not subscribe to “Rivista … ,” you may find this at:  .

A case may be made that DNAmation increases during sleep.  My explanation of sleep is that DHEA is high during consciousness and low during sleep.  

It is also my hypothesis of 1985 that the “fight or flight mechanism” is based on the ratio of DHEA to cortisol.  That is, I think DHEA levels determine the amount of motivation an organism brings to a confrontation and cortisol evolved to counteract the effects of DHEA.  If cortisol is high enough, then an organism avoids the consequences of a confrontation such as loss of blood, infection, ...death.  Evolution would quickly select this mechanism as it would promote future reproduction of more organisms and fighting would reduce reproduction.

This is derived from my examination of the adrenal hormone pathways in 1984.  It became apparent to me quickly that there really are mainly two pathways of major amounts of hormone production, that is, DHEA and cortisol.  This ratio directly affects gene activation, so, physiology and behavior are affected.

A case may be made that cortisol is connected with increased DNAmation.

In 1985, I first suggested that low DHEA is involved in depression, HIV AIDS (not called this at the time), Alzheimer's disease, aging, etc.  All of these express increased DNAmation.

It is also my hypothesis that low DHEA is involved in cancer initiation. In 1994, I first suggested that low DHEA is directly involved in initiation of oncogenes: “An Explanation of Cancer and the Increase in Cancer: High Testosterone, Low DHEA and Breast Cancer,” at: which appeared first in publication: (Annals of Internal Medicine 2005; 142: 471-472 .) “It is commonly known that inactivation of certain tumor-suppressor genes occurs as a consequence of hypermethylation within the promoter regions and a numerous studies have demonstrated a broad range of genes silenced by DNA methylation in different cancer types.” (Adv Genet. 2010;70:27-56)

I think DHEA was selected by evolution to increase gene expression.

I suggest that low dehydroepiandrosterone increases DNA methylation.  This mechanism was selected by evolution to reduce gene activity during sleep.