Neuroendocrine biomarkers of aging in the rat.

The genome and environmental agents are believed to regulate aging processes mainly via the homeostatic and integrative mechanisms of the body, which consist primarily of the neuroendocrine, immune and cell-to-cell communicating systems. Of these, the neuroendocrine system is considered to be the most important since it regulates to a greater or lesser degree all body functions, in old age as well as in early and mature life. We have studied mainly three aging events in the rat: the reproductive decline, development of numerous mammary and pituitary tumors and the decrease in GH secretion and protein synthesis. We have found that all three are caused primarily by faults that develop in hypothalamic function, particularly the decline in norepinephrine (NE) and dopamine (DA) activity. This decline appears to be caused largely by damage to hypothalamic neurons as a result of the chronic action of hormones, toxins, free radicals, cross linkages, lipofuscin accumulation and "wear and tear". Administration of drugs that increase hypothalamic NE and DA activity can delay or reverse all three aging events. Changes in hormone secretion, estrous cycles, tumor development and protein synthesis can be measured and used as "biomarkers of aging" in the rat.