Hypothalamic Regulatory Mechanisms of Aging

The hypothalamus is the most important integrator of functions of the autonomous, endocrine, somatic nervous systems; it is involved in the regulation of rhythmic processes and systemic aging. Putative hypothalamic nuclei responsible for the implementation of the developmental program of aging include the suprachiasmatic nucleus and the median group of nuclei, including the arcuate, ventromedial, and dorsomedial nuclei. Hypothalamic aging is accompanied by an excitation-inhibition imbalance due to dysregulation of the GABAergic system, decreased frequency of neuronal firing, impaired calcium metabolism, elevated nitric oxide production, decreased autophagy, and disturbed intracellular signaling, in particular Sirt1, mTOR, NF-kappa B, AMPK, P53, and FoxO. Also, an important role in hypothalamic aging belongs to specialized ependymal cells, tanycytes, as manifested in the disruption of tanycyte-neuron relationships and impaired barrier function of these cells. Hypothalamic neural stem cells, located mainly in the region of the middle hypothalamic nuclei, secrete exosomal microRNA also responsible for anti-aging effects of stem cells. The pool of hypothalamic neural stem cells, as well as microRNA production therein, decline with age.