Why There are Two Peaks of Death and Disease in Older Age
Copyright, 2004, James Michael Howard,
It is my hypothesis that DHEA was selected by evolution because it optimizes replication and transcription of DNA. Therefore, all genes and tissues are activated by DHEA. I think the rise of DHEA caused the evolution of mammals (Hormones in Mammalian Evolution, Rivista di Biologia / Biology Forum 2001; 94: 177-184). DHEA production may be involved in the pattern described by Dr. Steven Frank: "Humans die at an increasing rate until late in life, when mortality rates level off." (“A Multistage Theory of Age-specific Acceleration in Human Mortality,” BMC Biology 2004; 2: 16, an online journal)
DHEA is very high through the first month of life, followed by a severe decline until ages 5-7 years (adrenarche), whereupon it increases rapidly until age 20-25 years, then declines again, reaching very low levels in old age.
I suggest this represents the onset of neonatal production of DHEA which triggers rapid growth and development, especially in the brain. This rapid growth of the brain causes the decline of "measurable" levels of DHEA prior to adrenarche. The brain literally absorbs the available DHEA for growth and development. Once the brain begins to finalize growth and development, measurable levels of DHEA reappear and adrenarche begins. This frees DHEA for growth and development of the body, which, when near completion, again allows DHEA for activation of the brain centers which control puberty. (This is the basis for a switch from growth and development to activation and maintenance.) Availability of DHEA is first used for the brain, then the body, and is then used for activation of puberty. DHEA continues production until our reproduction is completed, then it declines. There is no need to continue DHEA production after reproduction and children are able to exist without parents. DHEA production begins to decline thereafter; activation of all tissues declines correspondingly. I think the loss of DHEA results in aging. (DHEA declines in AIDS; I think AIDS represents premature aging because of this abnormal decline of DHEA.)
The decline of DHEA reduces the activity level of all tissues. (I think the brain is especially able to use DHEA so the brain, usually, declines last. Remember the hypothetical use of DHEA for growth and development of the brain.) As an individual’s genome contains genes that differ from that state most optimal for maintenance of the person, the decline of DHEA will expose them, again, correspondingly. That is, declining levels of DHEA are less able to participate in activation of genes that differ from optimal configuration for transcription. These genes then increase the probability of consequences of gene loss. These consequences are exposed as DHEA declines. Many diseases and disorders manifest themselves with age. Some of these cause death.
If a person does not carry genes that are prone to malfunction during DHEA decline, then that person will live beyond the average age of individuals who carry genes prone to the dire consequences of DHEA decline. These people exhibit the “normal” life span dependent upon DHEA production. At some point in old age, DHEA declines to the point that brain function fails to maintain cardiovascular function.
I suggest the “early-life increase and late-life decrease in mortality acceleration” may be explained by this combination of DHEA decline in individuals with genes prone to malfunction and individuals who do not carry these genes.