Connections of SAMP8 Mice, Growth Hormone, Ageing, and DHEA
Copyright 2011, James Michael Howard, Fayetteville, Arkansas, U.S.A.
It is my hypothesis that evolution selected DHEA because it optimizes replication and transcription of DNA. Therefore DHEA levels affect all tissues and all tissues and genes compete for available DHEA. Furthermore, subordinate to this hypothesis is my hypothesis that DHEA acts with proteins which affect replication and transcription of DNA. The specificity and timing of these hormones will direct sequential gene activity and, therefore, direct growth and differentiation of all tissues. Some of these proteins will affect use of DHEA more than others, that is, some proteins will affect DNA more broadly than others. For example, I think growth hormone acts more broadly than a more specific protein such as a nerve growth factor. A protein that acts more broadly will "use" DHEA more than a more specific transcription factor.
It follows that loss of DHEA accelerates the loss of replication and transcription of DNA, that is, loss of DHEA accelerates ageing and ageing-associated phenomena, including loss of telomerase ("Telomeres, Telomerase, Dehydroepiandrosterone, and Cancer and Aging," at: http://anthropogeny.com/Telomeres.htm ).
I suggest the "senescence-accelerated mouse" may exist because of decreased DHEA. The "SAMP8" mouse is considered a possible animal model of Alzheimer's disease. While no research has examined the levels of DHEA in SAMP8 mice, one citation exists which demonstrates that DHEAS, the precursor of DHEA, is "more effective in reversing the cognitive impairments" in a SAMP8 study (Life Sci. 2004 Oct 22;75(23):2775-85). Loosely, this may support low DHEA in this animal model. I first suggested low DHEA as a cause of Alzheimer's disease in 1985 (copyrighted).
When the foregoing is combined, an explanation of Banks, et al., Proceedings of the National Academy of Science U S A. 2010 Dec 21;107(51):22272-7, "Effects of a growth hormone-releasing hormone antagonist on telomerase activity, oxidative stress, longevity, and aging in mice," may be produced. If SAMP8 mice are deficient in DHEA, then administration of growth hormone will further reduce available DHEA, that is, growth hormone will accelerate ageing, and other problems of loss of DHEA, in individuals of low DHEA. This may explain why "These results strongly suggest that growth hormone, when given to middle aged and older people, may be hazardous." (http://www.medicalnewstoday.com/articles/212470.php). Now, if I am correct, using "growth hormone-releasing hormone (GHRH) antagonist" (previous url) will positively affect SAMP8 mice because reducing the use of DHEA by growth hormone will increase use of DHEA by other, specific growth factors, such as those used by the brain. That is, in the competition among tissues and genes for DHEA, Banks, et al., shifted the "winner."