The importance of being dehydroepiandrosterone sulfate (in the blood of primates): a longer and healthier life?

The general aging sequence in tissues of healthy human beings is proposed to be: capillary endothelial cell damage --> arteriosclerosis --> decreased blood flow --> metabolic dysregulation --> secondary tissue damage. Molecular O2 is an obligatory substrate for the successive syntheses of 17alpha-OH pregnenolone and dehydroepiandrosterone (DHEA) by cytochrome P450c17 in the zona reticularis of the adrenal cortex, in which it is suggested that arteriosclerosis --> decreased blood flow --> O2 and glucose deficit --> decreased O2-requiring synthesis of DHEA --> eventual decrease in number of DHEA-synthesizing cells. Aging changes in the zona reticularis synergize with those in the hypothalamo-hypophyseal machinery that controls it neurally and hormonally, with ACTH-evoked pulsatile floods of cortisol coming from the adrenal zona fasciculata, with the onslaught of free radicals generated by the metabolism of catecholamines released from interdigitating cells of the adrenal medulla, and with age-correlated disabilities of erythrocytes to bind and release O2 to decrease the viability of the DHEA and dehydroepiandrosterone sulfate (DHEAS)-forming cells. One of the chief functions of serum DHEAS in the male may be to act as an allosteric facilitator of the binding of testosterone (T) to serum albumin, thereby helping target T to specific receptors and to allosteric sites for rapid and efficient action at the cellular level. There is reason to consider combining O2 therapy with appropriate administration of DHEA and T to optimize steroid functionality in the healthy aging male, and thus, possibly, to alleviate some of the age-related cognitive and physical decrements that occur.