New Encyclopedia of Neuroscience. Elsevier (2007) Neuroendocrine Aging: Pituitary–Metabolism
Sonntag W.E. , Herenu C.B. and Goya R.G.
I. Overview
A substantial volume of empirical and scientific evidence has accumulated demonstrating that biological aging is associated with functional deficits at the cellular, tissue, organ and system levels. Several theories have been proposed to explain these changes as well as the increased risk of disease with age. However, to date, no single explanation has satisfactorily accounted for the diversity of effects related to biological aging and it is apparent that several factors interact resulting in the decline in tissue function. Current concepts of aging encompass free radical, somatic mutation, error,
The neuroendocrine theory of aging evolved from observations that animals exhibit predictable and progressive impairments in a number of physiological progresses with time including, but not limited to, decreases in reproductive and immune function, decreases in muscle mass and function, accumulation of adipose tissue, and decreases in glucose utilization and cognitive function. The role of the neuroendocrine system in these processes was related to the observation that many of the hormones regulated by the neuroendocrine system had an important trophic and integrative role in maintaining tissue function and that withdrawal of hormonal support mimicked some of the phenotypes observed in aging animals and humans.
The neuroendocrine system includes the hypothalamus and associated brain structures as well as the pituitary gland. This system includes neurotransmitters and neuropeptides within the brain that regulate hypothalamic-releasing and inhibiting hormones secreted into hypophysial portal blood that reaches the pituitary gland. The release of these hormones influences the secretion of anterior pituitary hormones into the bloodstream and subsequently regulates tissue function. The posterior pituitary also is an important part of the neuroendocrine system but, in contrast to the anterior pituitary gland, is composed of long axons from specific hypothalamic nuclei. The hypothalamus and pituitary gland have the capacity to detect neural activity and/or humoral secretions from target tissues and adjust activity to maintain an optimal internal environment or ‘milieu’ for tissue function. It is well-established that the neuroendocrine system has a critical role in regulating tissue growth and metabolism through the release of growth hormone and thyroid stimulating hormone, reproductive function through the release of luteinizing hormone (LH), Follicle stimulating hormone (
Although the etiology of the age-related changes in the neuroendocrine system are unknown, it has been proposed that cellular and molecular events in specific subpopulations of neurons within the hypothalamus and brain and/or supporting structures are a contributing factor in the dysregulation of this system. The cause of the specific perturbations may be related to genetic errors or increased free radicals that lead to progressive aberrations in tissue function. As a result, the neuroendocrine theory of aging is unique compared to other theories of aging in that alterations in this system are not considered the primary causative factor in biological aging but rather are important mediators of aging initiated by cellular changes in specific subpopulations of neurons or systems that closely interact with hypothalamic neurons. In this brief synopsis the major alterations within the neuroendocrine axis are discussed with special emphasis on the regulation of growth hormone since it exhibits some of more important physiological changes that occur with age.