Nature of altered pulsatile hormone release and neuroendocrine network signalling in human ageing: Clinical studies of the somatotropic, gonadotropic, corticotropic and insulin axes

Recent clinical investigations have implemented an array of new analytical tools to evaluate the neuroregulation of endocrine axes. These studies demonstrate multifold disruption within the growth hormone (GH), luteinizing hormone (LH)-testosterone, adrenocorticotropin (ACTH)-cortisol and the insulin axes in healthy ageing men and women. Novel research strategies in ageing include such developments as the indirect in vivo assessment of neuroendocrine network integration, via the approximate entropy (ApEn) statistic to monitor the unihormonal orderliness and bihormonal synchronicity of hormone release, and thus infer stability of network-integrative processes. For example, ApEn calculations show that the individual orderliness of GH, insulin or LH release falls progressively in older men and women, and the conditional synchrony between LH and testosterone (or LH and follicle-stimulating hormone/prolactin) release, and LH secretion and the neurogenically organized signal, nocturnal penile tumescence (NPT), all decline markedly in older men. Evaluation of the ACTH-cortisol axis points additionally to disrupted bihormonal synchrony within this stress-responsive system in healthy ageing. A complementary investigative tool, viz. a stochastic differential equation random-effects feedback construct of the interactive male gonadotropin-releasing hormone-LH-testosterone axis, predicts that only certain extant postulates of ageing in the male reproductive axis will give rise to the observed erosion of LH-testosterone synchrony. Collectively, available clinical data suggest a general model of early neuroendocrine ageing in the human, in both the male and female, wherein ageing is marked by variable disruption in the time-delayed feedback and feedforward interconnections among neuroendocrine glands, which constitute an integrated axis and which control the joint synchrony of hormone release.