The hypothalamus is a collection of distinct neurosecretory cells located at the base of the brain. These neurosecretory cells receive a multitude of external and internal signals from virtually all organs in the form of hypothalamus-end-organ axes. They interpret, integrate, and respond to these messages accordingly and maintain homeostasis in the body. The vital processes under control of the hypothalamus include regulation of body temperature, nutrient intake and energy balance, sleep and wake cycle, sexual behavior, reproductive cyclicity, water and electrolyte balance, stress adaptation, nursing, growth, and circadian or ultradian cycles. When the responsiveness of these neurons declines during aging, all body activities are adversely affected.
Hypothalamus and pituitary are closely related structures with the major role of integrating neural and endocrine systems. The hypothalamic – pituitary–adrenal (HPA) axis is responsible for the synthesis and release of steroid hormones, the most abundant being dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), cortisol and aldosterone.
The hypothalamus plays a key role in regulating metabolism. Consequently, an understanding of the effects of aging on the hypothalamus may provide important insights into the organismal aging process. For example, it has been shown that neuroendocrine regulation of insulin signaling affects longevity in C. elegans. In mammals, hypothalamic modulation of the neuroendocrine system may regulate the aging process by controlling the production, processing, and degradation of neuroendocrine hormones and neuropeptides. A number of key genes involved in neuronal structure and signaling are differentially expressed in both the aged hypothalamus and cortex, including synaptotagmin I, cAMP-dependent protein kinase C β, apolipoprotein E, protein phosphatase 2A, and prostaglandin D. Misregulation of these proteins may contribute to age-related memory deficits and neurodegenerative diseases. In addition, many proteases that play essential roles in regulating neuropeptide metabolism, amyloid precursor protein processing, and neuronal apoptosis are up-regulated in the aged brain and likely contribute significantly to brain aging.