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      Longevity and compression of morbidity from a neuroscience perspective: Do we have a duty to die by a certain age?

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          Abstract

          The search for longevity, if not for immortality itself, has been as old as recorded history. The great strides made in the standard of living and the advances in scientific medicine, have resulted in unprecedented increases in longevity, concomitant with improved quality of life. Thanks to medical progress senior citizens, particularly octogenarians, have become the fastest growing segment of the population and the number of centenarians is increasing, even though in the last two decades, spurred by the bioethics movement, the priority assigned to the prolongation of lifespan has taken a back seat to the containment of health care costs. This article describes what individuals can do to lead healthy lifestyles and increase longevity, concomitant with preservation of quality of life until the very end of life—as postulated by Dr. James F. Fries’ hypothesis of the compression of morbidity. This review article investigates the contention of bioethicist Dr. Ezekiel Emanuel that Fries’ theory is a “fantasy” and not a realistic possibility. In this context recent advances in neurobiology, epigenetics, and aging are described, and the hypothesis of the compression of morbidity re-examined. We find that people are not only living longer but are remaining healthier. Recent studies suggest that brain plasticity develops and potential neurogenesis occurs in those individuals who continue to be mentally and physically active allowing them to thrive well into old age. Controlled studies as well as Medicare spending data strongly corroborate Fries’ predictions and support my conclusion that compression of morbidity should be upgraded from a hypothesis to a theory. Lastly, leisure in association with or without retirement is discussed and suggestions are made as to how to use this time to remain intellectually sharp and physically vigorous until the very end of life.

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          Most cited references48

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          Brain-derived neurotrophic factor/TrkB signaling in memory processes.

          Activity-dependent changes in synaptic strength are considered mechanisms underlying learning and memory. Brain-derived neurotrophic factor (BDNF) plays an important role in activity-dependent synaptic plasticity such as long-term potentiation. Recent experimental evidence supports the role of BDNF in memory processes: Memory acquisition and consolidation are associated with an increase in BDNF mRNA expression and the activation of its receptor TrkB. Genetic as well as pharmacologic deprivation of BDNF or TrkB impairs learning and memory. In a positively motivated radial arm maze test, activation of the TrkB/phosphatidylinositol-3 kinase (PI3-K) signaling pathway in the hippocampus is associated with consolidation of spatial memory through an activation of translational processes. In a negatively motivated passive avoidance test, mitogen-activated protein kinase (MAPK) is activated during acquisition of fear memory. Furthermore, recent findings suggest the importance of interaction between BDNF/TrkB signaling and NMDA receptors for spatial memory. A Src-family tyrosine kinase, Fyn plays a role in this interaction by linking TrkB with NR2B. These findings suggest that BDNF/TrkB signaling in the hippocampus plays a crucial role in learning and memory.
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            Aging, health risks, and cumulative disability.

            Persons with lower health risks tend to live longer than those with higher health risks, but there has been concern that greater longevity may bring with it greater disability. We performed a longitudinal study to determine whether persons with lower potentially modifiable health risks have more or less cumulative disability. We studied 1741 university alumni who were surveyed first in 1962 (average age, 43 years) and then annually starting in 1986. Strata of high, moderate, and low risk were defined on the basis of smoking, body-mass index, and exercise patterns. Cumulative disability was determined with a health-assessment questionnaire and scored on a scale of 0 to 3. Cumulative disability from 1986 to 1994 (average age in 1994, 75 years) or death was the measure of lifetime disability. Persons with high health risks in 1962 or 1986 had twice the cumulative disability of those with low health risks (disability index, 1.02 vs. 0.49; P<0.001). The results were consistent among survivors, subjects who died, men, and women and for both the last year and the last two years of observation. The onset of disability was postponed by more than five years in the low-risk group as compared with the high-risk group. The disability index for the low-risk subjects who died was half that for the high-risk subjects in the last one or two years of observation. Smoking, body-mass index, and exercise patterns in midlife and late adulthood are predictors of subsequent disability. Not only do persons with better health habits survive longer, but in such persons, disability is postponed and compressed into fewer years at the end of life.
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              Microglia-mediated immunoexcitotoxicity, a key player in traumatic brain injury?

              Some individuals suffering from mild traumatic brain injuries, especially repetitive mild concussions, are thought to develop a slowly progressive encephalopathy characterized by a number of the neuropathological elements shared with various neurodegenerative diseases. A central pathological mechanism explaining the development of progressive neurodegeneration in this subset of individuals has not been elucidated. Yet, a large number of studies indicate that a process called immunoexcitotoxicity may be playing a central role in many neurodegenerative diseases including chronic traumatic encephalopathy (CTE). The term immunoexcitotoxicity was first coined by the lead author to explain the evolving pathological and neurodevelopmental changes in autism and the Gulf War Syndrome, but it can be applied to a number of neurodegenerative disorders. The interaction between immune receptors within the central nervous system (CNS) and excitatory glutamate receptors trigger a series of events, such as extensive reactive oxygen species/reactive nitrogen species generation, accumulation of lipid peroxidation products, and prostaglandin activation, which then leads to dendritic retraction, synaptic injury, damage to microtubules, and mitochondrial suppression. In this paper, we discuss the mechanism of immunoexcitotoxicity and its link to each of the pathophysiological and neurochemical events previously described with CTE, with special emphasis on the observed accumulation of hyperphosphorylated tau.
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                Author and article information

                Contributors
                Journal
                Surg Neurol Int
                Surg Neurol Int
                SNI
                Surgical Neurology International
                Medknow Publications & Media Pvt Ltd (India )
                2229-5097
                2152-7806
                2015
                30 March 2015
                : 6
                : 49
                Affiliations
                [1]Clinical Professor of Neurosurgery (ret.) and Adjunct Professor of Medical History (ret.), Mercer University School of Medicine, Macon, Georgia, USA
                Author notes
                [* ]Corresponding author
                Article
                SNI-6-49
                10.4103/2152-7806.154273
                4392568
                6408f34a-8524-4a6d-8dbf-6bf69c705c27
                Copyright: © 2015 Faria MA.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 04 January 2015
                : 14 January 2015
                Categories
                Review Article

                Surgery
                bioethics,brain plasticity,compression of morbidity,end of life,healthy lifestyles,longevity
                Surgery
                bioethics, brain plasticity, compression of morbidity, end of life, healthy lifestyles, longevity

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