The Hanson Releasing Hormone Depletion Theory of Aging

A fundamental concept of cell biology, and the reason multicellular organisms exist, is symbiosis. Early in the evolution of life, some cells were able to specialize in function when other cells evolved to work in concert with the specialized cells. One of the most important symbiotic relationships in higher organisms is the relationship between neurons and glial cells.

The hypothalamus is a region of the brain that is known to contain neurons that produce releasing hormones. Other regions have been identified that also have peptidergic neurons. Hypothalamic releasing hormones travel to the pituitary and stimulate the production of hormones. When peptidergic neurons die, their place in the matrix is filled by glial cells. Even if neurons could de-differentiate and undergo mitosis, they could not compete with the glial cells, which almost immediately fill in the matrix. Over time, the number of neurons secreting the releasing hormones, decreases. The concentration gradient of releasing hormones reaching endocrine glands decreases. The result is decreased production of hormones.

Of particular importance may be the decreasing concentration gradient of PACAP over time. The physiological systems in an organism that decrease in activity over time are most associated with aging. But some systems do not change over time, and some actually increase. There exists a strong positive correlation between the second-messenger system a cell uses, and whether the cell up-regulates, stays the same, or down-regulates over time. The systems that decrease over time use the cyclic amp second-messenger system for cellular control. I believe the decreasing concentration of PACAP resulting from decreased pituitary output results in this down-regulation of cellular systems.

PACAP, however, is not the only hormone effecting the activity of cellular systems over time. There are perhaps 50 different molecules working together and to isolate and study the effects of just one, would miss the big picture. If hormone replacement therapy is to be effective, a shotgun approach would be the best one.

Research should be done to test my theory that releasing hormone depletion results in the physiological effects of aging. A suitable test organism should be chosen. Stem cells should then be injected into the hypothalamic region and mitosis in the hypothalamic glial cells should be blocked. Other regions that produce releasing hormones should be investigated.

©  David A. Hanson,