During the past five decades, a myriad of animal experiments has suggested that DHEA is a multifunctional hormone with immunoenhancing, antidiabetic, antiobesity, anticancer, neurotropic, memory-enhancing, and antiaging effects. Recently, P450c17 expression and biosynthesis of DHEA were found to interact by way of a tripartite contribution of astrocytes, oligodendrocytes, and neurones. These neurosteroids act as an antagonist of the aminobutyric acid type A receptor and as a modulator of the N-methyl-D-aspartate receptor and may have sleep inducing (rapid eye movement sleep), memory enhancing, and anxiolytic properties. DHEA is a multifunctional hormone with beneficial effects, including antiaging properties.
The secretion of DHEA by the human adrenal gland exhibits a pulsatile pattern with increasing frequency and amplitude at night. This pattern of DHEA synthesis and secretion by the zona reticularis is, in large measure, mediated by corticotrophin (ACTH) but without the feedback regulatory function. With ageing, the progressive blunting of ACTH mediates pulsatile activities, particularly the nocturnal amplification of DHEA, without affecting the pulsatile rhythm of cortisol. Although the decline of DHEAS levels persists into advanced age with a sexually dimorphic pattern, in contrast, cortisol levels in men and women show a parallel linear increase with aging. The age-related decline in DHEAS shows marked individual differences with a wide range of values and is under partial hereditary control. It has been suggested that DHEAS may be a measurable component of the individuality of the aging process itself.
Fig.1 Dehydroepiandrosterone (DHEA)
The biological function of DHEA and DHEAS in human aging is evolving.
It was concluded that in aging men, but not in aging women, low DHEAS levels are a reliable predictor of death in smokers, even in former smokers, under 70 years of age.
In human aging, the reduction of adrenal androgen secretion is accompanied by a host of neuroendocrine-metabolic dysfunctions that include decline in the growth hormone (GH)-insulin-like growth factor I (GH-IGF-I) system, thyroid function, and immune competence, fragmentation of sleep, and neuronal loss.
Low DHEAS levels are a reliable predictor of death in male smokers, but smokers are associated with high instead of the low DHEAS levels observed?
Among the oldest men, those with the highest functional status had the highest DHEAS levels, and individuals with poor functioning levels had the lowest DHEAS levels.
For example healthy centenarians plasma IGF-I/IGF-binding protein 3 (IGFBP3) molar ratios are greater than in aged subjects, suggesting increased bioavailable IGF-I might improve insulin action and plasma lipid profiles in centenarians.
Thus, DHEAS may serve as important endogenous regulator of hepatic PPAR-mediated pathways thereby maintain lipid homeostasis and prevent decline in cellular PPAR expression in normal aging.
In humans, scientists have provided evidence that serum levels of IL-6 increase with age and that serum DHEAS levels are negatively correlated with serum IL-6 concentrations in both aging men and women. The maximal effective dose of DHEA is in the range for immunomodulation. Thus, the increase in IL-6 production during the process of aging might be related to diminished DHEAS secretion, which, in turn, may be a significant cofactor for the manifestation of inflammatory and age-related diseases, including bone loss.
If DHEA has been taken before bedtime to simulate the circadian rise of DHEA secretion at night then it was noticed that DHEA administration (50 mg/day) induced an impressive improvement in well-being, depression score, and sexual interest in women with adrenal insufficiency and very low endogenous DHEA levels. Beneficial effects of DHEA have been found in immune function in controlled studies in postmenopausal women and in systemic lupus erythematosus. Nighttime DHEA administration targeted to individuals with low DHEAS levels would likely afford maximal benefits, e.g., improved quality of sleep and increase in muscle strength. Cessation of smoking and the supplementation of low DHEA levels may be a most sound approach to reducing mortality in male smokers.