The present update highlights the impact of age on dynamic regulatory changes arising singly and multiply within several prototypical neuroendocrine axes in the human. A neuroendocrine axis is viewed here as a homeostatic unit maintained by multivalent interactions or network-like integration among CNS-hypothalamic, pituitary, and target-tissue sites; for example, the GHRH/somatostatin-GH-IGF-I, GnRH-LH-sex-steroid and CRH/AVP-ACTH-cortisol feedback-controlled axes. Homeostatic control is driven by (time-lagged) interglandular signaling and dose-sensitive interfaces. According to this broader perspective, a neuroendocrine system operates as an interdependent ensemble of reciprocally communicating control nodes. This dynamic precept provides a foundation for identifying among the earliest vivid features of signaling disruption within the somatotropic, gonadotropic, and corticotropic (as well as insulinotropic) axes in healthy aging men and women. Internodal linkages likely deteriorate further in the face of acute or chronic illness, medication use, systemic stress and/or hospitalization, resulting at times in overt failure of neuroglandular output. This extended concept offers a notion of neuroendocrine axis frailty as a precursor to frank endocrine-system disability in aging. Such a framework also confers the expectation that pluri- or multiaxis disruption (e.g., combined somatotropic and gonadal) would further adversely impact homeostatic vigor in aging individuals.
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