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Possible new breakthroughs in understanding the aging mind that can be used to benefit older people are now emerging from research. This volume identifies the key scientific advances and the opportunities they bring. For example, science has learned that among older adults who do not suffer from Alzheimer's disease or other dementias, cognitive decline may depend less on loss of brain cells than on changes in the health of neurons and neural networks. Research on the processes that maintain neural health shows promise of revealing new ways to promote cognitive functioning in older people. Research is also showing how cognitive functioning depends on the conjunction of biology and culture. The ways older people adapt to changes in their nervous systems, and perhaps the changes themselves, are shaped by past life experiences, present living situations, changing motives, cultural expectations, and emerging technology, as well as by their physical health status and sensory-motor capabilities. Improved understanding of how physical and contextual factors interact can help explain why some cognitive functions are impaired in aging while others are spared and why cognitive capability is impaired in some older adults and spared in others. On the basis of these exciting findings, the report makes specific recommends that the U.S. government support three major new initiatives as the next steps for research.
Neuroregulatory Mechanisms in Aging.
An animal’s survival strongly depends on its ability to maintain homeostasis in response to the changing quality of its external and internal environments. This is achieved through intercellular communication not only within a single tissue but also among different tissues and organ systems. Thus, alterations in tissue-to-tissue or organ-to-organ communications, which are under genetic regulation, can affect organismal homeostasis, and consequently impact the aging process. One of the organ systems that play a major role in maintaining homeostasis is the nervous system. Considering that the nervous system includes the sensory system, which perceives the complexity of an animal’s environment, it should be no surprise that there would be a sensory influence on homeostasis and aging. To promote homeostasis, any given sensory information is transmitted through short-range signals via neural circuits and/or through long-range endocrine signals to target tissues, which may in turn be neuronal or non-neuronal in nature. At the same time, since homeostasis involves a number of feedback mechanisms, non-neuronal tissues can also modulate sensory and other neuronal functions. Several genes that regulate signaling pathways known to affect homeostasis and aging have been shown to act in neurons, in tissues that are likely downstream targets of the nervous system, or through feedback regulation of neuronal activities. These genes can have different temporal requirements: some might function early, e.g., by affecting neural development, while others may only be required later in adulthood. Some well-known examples of genes involved in the neuronal regulation of homeostasis and longevity encode components of the evolutionarily conserved nutrient-sensing insulin/insulin-like signaling pathway, the stress-sensing internal repair system, and the mitochondrial electron transport chain. Indeed, the genetic perturbation of these pathways has been found to lead to numerous diseases, many of which are age-related and involve the nervous system, such as neurodegeneration and the metabolic syndrome. Despite much progress, however, many aspects of the neuronal inputs and outputs that affect aging and longevity are poorly understood to date. For example, the precise neuronal and non-neuronal circuitries and the details of the molecular mechanisms through which genes/signaling pathways maintain homeostasis and affect aging in response to the environment remain to be elucidated. Similarly, it is presently unclear whether genes that regulate the early development of the nervous system and its consequent circuitry influence homeostasis and longevity during adulthood. At the same time, although many genes affecting aging are conserved, both the nervous system and the aging process are highly variable within populations and among taxa. Accordingly, the role of natural genetic variation in shaping the neurobiology of aging is also presently unknown. The aim of this Research Topic is therefore to highlight the genetic, developmental, and physiological aspects of the signaling networks that mediate the neuronal inputs and outputs that are required to maintain organismal homeostasis. The elucidation of the effects of these neuronal activities on homeostasis may thus provide much-needed insight into mechanisms that affect aging and longevity.
Development and Aging in the Nervous System covers the proceedings of a series of symposia by the same title, held at the University of Miami Training Program in Cellular Aging on February 19-20, 1973. This book is composed of 11 chapters that specifically consider aging in its total sense, from embryonic development through senescence of a vital organ system of the body. The introductory chapters review the age changes in the neuronal microenvironment and the regulative mechanism of neuronal death in cell number control in the nervous system. The next chapters deal with the neuronal degeneration in aging mammals, the selected changes in the developing postnatal rat, and the trophic influences in the mammalian central nervous system. These topics are followed by discussions of the genesis of neuronal locus specificity, the vertebrate brain aging, and the neurochemical patterns in the developing and aging brain. The remaining chapters describe the mechanisms of enzymatic differentiation in the brain and in cultured cells and the monoamine metabolism in the aging male mouse. This book will prove useful to development and cell biologists, researchers, and advance students.