Showing papers on "Aging brain published in 2007"

Hippocampal Expression Analyses Reveal Selective Association of Immediate-Early, Neuroenergetic, and Myelinogenic Pathways with Cognitive Impairment in Aged Rats

Abstract: Although expression of some genes is known to change during neuronal activity or plasticity, the overall relationship of gene expression changes to memory or memory disorders is not well understood. Here, we combined extensive statistical microarray analyses with behavioral testing to comprehensively identify genes and pathways associated with aging and cognitive dysfunction. Aged rats were separated into cognitively unimpaired (AU) or impaired (AI) groups based on their Morris water maze performance relative to young-adult (Y) animals. Hippocampal gene expression was assessed in Y, AU, and AI on the fifth (last) day of maze training (5T) or 21 d posttraining (21PT) and in nontrained animals (eight groups total, one array per animal; n = 78 arrays). ANOVA and linear contrasts identified genes that differed from Y generally with aging (differed in both AU and AI) or selectively, with cognitive status (differed only in AI or AU). Altered pathways/processes were identified by overrepresentation analyses of changed genes. With general aging, there was downregulation of axonal growth, cytoskeletal assembly/transport, signaling, and lipogenic/uptake pathways, concomitant with upregulation in immune/inflammatory, lysosomal, lipid/protein degradation, cholesterol transport, transforming growth factor, and cAMP signaling pathways, primarily independent of training condition. Selectively, in AI, there was downregulation at 5T of immediate-early gene, Wnt (wingless integration site), insulin, and G-protein signaling, lipogenesis, and glucose utilization pathways, whereas Notch2 (oligodendrocyte development) and myelination pathways were upregulated, particularly at 21PT. In AU, receptor/signal transduction genes were upregulated, perhaps as compensatory responses. Immunohistochemistry confirmed and extended selected microarray results. Together, the findings suggest a new model, in which deficient neuroenergetics leads to downregulated neuronal signaling and increased glial activation, resulting in aging-related cognitive dysfunction.

Brain aging : models, methods, and mechanisms

Abstract: Assessing Cognitive Aging Changes in Cognitive Function in Human Aging, E. L. Glisky Successful vs. Unsuccessful Aging in Rhesus Monkeys, M.B. Moss, T. L. Moore, S.P. Schettler, R. Killiany, and D. Rosene Neuropsychology of Cognitive Aging in Rodents, J. S. Rodefer and M. G. Baxter Quantifying Aging-Related Changes in the Brain Design-Based Stereology in Brain Aging Research, C. Schmitz and P.R. Hof The Effects of Normal Aging on Nerve Fibers and Neuroglia in the Central Nervous System, A. Peters Neurogenesis in the Adult and Aging Brain, D.R. Riddle and R.J. Lichtenwalner Expression Profile Analysis of Brain Aging, S.D. Ginsberg, Ph.D. Assessing Functional Changes in the Aging Nervous System Subtle Alterations in Glutamatergic Synapses Underlie the Aging-Related Declines in Hippocampal Functions, L. Shi, M. Adams, and J. Brunso-Bechtold Assessment of Second Messenger Function in the Hippocampus of Aged Rats with Cognitive Impairment, M.M. Nicolle, H.Y. Zhang, and J. L. Bizon Neurophysiology of Old Neurons and Synapses, A. Kumar and T. C. Foster Imaging Cognition in the Aging Human Brain, T. Hedden Mechanisms Contributing to Brain Aging Regulation of Cerebrovascular Aging, W.E. Sonntag, D.M. Eckman, J.Ingraham, and D.R. Riddle Stress and Glucocorticoid Contributions to Normal and Pathological Aging, K.A. Goosens and R.M. Sapolsky Altered Calcium Homeostasis in Old Neurons, E.C. Toescu Oxidative Stress and the Aging Brain: from Theory to Prevention, C.Gemma, Ph.D., J. Vila, A. Bachstetter, and P. C. Bickford, Ph.D. Index

Brain bank of the Brazilian aging brain study group - a milestone reached and more than 1,600 collected brains.

Abstract: Introduction Brain banking remains a necessity for the study of aging brain processes and related neurodegenerative diseases. In the present paper, we report the methods applied at and the first results of the Brain Bank of the Brazilian Aging Brain Study Group (BBBABSG) which has two main aims: (1) To collect a large number of brains of elderly comprising non-demented subjects and a large spectrum of pathologies related to aging brain processes, (2) To provide quality material to a multidisciplinar research network unraveling multiple aspects of aging brain processes and related neurodegenerative diseases.

The response of the aged brain to stroke: too much, too soon?

Abstract: Old age is associated with an enhanced susceptibility to stroke and poor recovery from brain injury, but the cellular processes underlying these phenomena are only recently coming to light. Potential mechanisms include changes in brain plasticity-promoting factors, unregulated expression of neurotoxic factors, or differences in the generation of scar tissue that impedes the formation of new axons and blood vessels in the infarcted region. Behaviorally, aged rats are more severely impaired by stroke than are young rats, and they also show diminished functional recovery. Infarct volume does not differ significantly in young and aged animals, but critical differences are apparent in the cytological response to stroke, most notably an age-related acceleration of the establishment of the glial scar. The early infarct in older rats is associated with a premature accumulation of BrdU-positive microglia and astrocytes, persistence of activated oligodendrocytes, a high incidence of neuronal degeneration, and accelerated apoptosis. Regeneration-associated mechanisms in the rat brain are active thoughout life, albeit at lower levels in the aged animals. However; after stroke in aged rats, neuroepithelial marker-positive cells emanating largely from capillaries did not make a significant contribution to neurogenesis in the infarcted cortex of aged animals. Furthermore, the expression of plasticity-associated proteins, such as MAP1B, was delayed in aged rats. Tissue recovery was further delayed by the upregulation of Nogo, ephrin-A5 and MAG, which exert a powerful negative effect on axonal sprouting in the aged peri-infarct cortex, and by an age-related increase in the amount of the neurotoxic C-terminal fragment of the β-amyloid precursor protein (βAPP) at 2 wks post-stroke. Our findings indicate that the aged brain has the capability to mount a cytoproliferative response to injury, but the timing of the cellular and genetic response to cerebral insult is dysregulated in aged animals, thereby further compromising functional recovery. Elucidating the molecular basis of this phenomenon in the aging brain could yield novel approaches to neurorestoration following stroke or head injury in the elderly.

The effects of aging, injury and disease on microglial function: a case for cellular senescence

Abstract: Neuroinflammation resulting from chronic reactive microgliosis is thought to contribute to age-related neurodegeneration, as well as age-related neurodegenerative diseases, specifically Alzheimer's disease (AD). Support of this theory comes from studies reporting a progressive, age-associated increase in microglia with an activated phenotype. Although the underlying cause(s) of this microglial reactivity is idiopathic, an accepted therapeutic strategy for the treatment of AD is inhibition of microglial activation using anti-inflammatory agents. Although the effectiveness of anti-inflammatory treatment for AD remains equivocal, microglial inhibition is being tested as a potential treatment for additional neurodegenerative disorders including amyotrophic lateral sclerosis and Parkinson's disease. Given the important and necessary functions of microglia in normal brain, careful evaluation of microglial function in the aged brain is a necessary first step in targeting more precise treatment strategies for aging-related neurodegenerative diseases. Studies from our laboratory have shown multiple age-related changes in microglial morphology and function that are suggestive of cellular senescence. In this manuscript, we review current knowledge of microglia in the aging brain and present new, unpublished work that further supports the theory that microglia experience an age-related decline in proliferative function as a result of cellular senescence.

Assessing the cognitive impact of Alzheimer disease pathology and vascular burden in the aging brain: the Geneva experience.

Abstract: The progressive development of Alzheimer disease (AD)-related lesions, such as neurofibrillary tangles (NFT), amyloid deposits and synaptic loss, and the occurrence of microvascular and small macrovascular pathology within the cerebral cortex are conspicuous neuropathologic features of brain aging Recent neuropathologic studies strongly suggested that the clinical diagnosis of dementia depends more on the severity and topography of pathological changes than on the presence of a qualitative marker However, several methodological problems, such as selection biases, case-control design, density-based measures and masking effects, of concomitant pathologies persisted In recent years, we performed several clinicopathologic studies using stereological counting of AD lesions In order to define the cognitive impact of lacunes and microvascular lesions, we also analyzed pure vascular cases without substantial AD pathology Our data revealed that total NFT numbers in the CA1 field, cortical microinfarcts and subcortical gray matter lacunes were the stronger determinants of dementia In contrast, the contribution of periventricular and subcortical white matter demyelinations had a modest cognitive effect even in rare cases with isolated microvascular pathology Importantly, in cases with pure AD pathology, more than 50% of Clinical Dementia Rating scale variability was not explained by NFT, amyloid deposits and neuronal loss in the hippocampal formation In cases with microvascular pathology or lacunes, this percentage was even lower The present review summarizes our data in this field and discusses their relevance within the theoretical framework of the functional neuropathology of brain aging and with particular reference to the current efforts to develop standardized neuropathological criteria for mixed dementia

Neuroinflammation and Parkinson's disease.

Abstract: Publisher Summary Parkinson's disease (PD) is the second most frequent neurodegenerative disorder of the aging brain after Alzheimer's dementia. Its clinical characteristics include resting tremor, slowness of movement, rigidity, and postural instability. This chapter reviews how inflammation is triggered in PD and which place it occupies in the sequence of events that ultimately leads to the demise of dopaminergic neurons. The chapter describes the composition of the inflammatory response in various parkinsonian syndromes, including PD per se as well as in animal models of PD. The potential beneficial and deleterious role of inflammation in PD and how it can be targeted for therapeutic purposes are also reviewed. Inflammation can involve any part of the body, including the brain. In many neurodegenerative diseases, the innate immune cells are activated and produce a variety of inflammatory mediators. There is often T-cell infiltration in affected brain areas in neurodegenerative diseases.

Altered expression of COX-2 in subdivisions of the hippocampus during aging and in Alzheimer's disease: the Hisayama Study.

Abstract: Background: It has been reported that nonsteroidal anti-inflammatory drugs may delay the onset of Alzheimer’s disease (AD). Since nonsteroidal anti-inflammatory drugs inhibit cyclooxygenase (COX), COX-2, an inducible form of COX, may be involved in the pathology of AD in association with the arachidonic acid cascade. In addition, it has been suggested that alterations in the balance of polyunsaturated fatty acids are associated with brain dysfunctions such as neurodegerative pathologies of the aging brain. Method: To explore COX-2 expression in the hippocampus, we analyzed 45 consecutive autopsy subjects without dementia and 25 AD patients derived from the town of Hisayama, Japan. Results: The neuronal expression of COX-2 in the CA3 subdivision of the hippocampus, subiculum, entorhinal cortex and transentorhinal cortex were consistently observed in both nondemented and AD brains, and COX-2 immunoreactivity correlated with age in nondemented brains. In AD patients, neurons of CA1 exhibited increased COX-2 immunoreactivity which correlated with the severity of AD pathology. This correlation was not apparent in nondemented subjects. Conclusion: These results suggest that COX-2 expression may be differentially regulated among subdivisions of the hippocampus and that elevated COX-2 expression in the CA1 of AD brains may be associated with AD pathology and thus cognitive dysfunction.

Impairment of long-term associative memory in aging snails (Lymnaea stagnalis).

Abstract: Age-dependent impairment in learning and memory functions occurs in many animal species, including humans. Although cell death contributes to age-related cognitive impairment in pathological forms of aging, learning and memory deficiencies develop with age even without substantial cell death. The molecular and cellular basis of this biological aging process is not well understood but seems to involve a decline in the aging brain's capacity for experience-dependent plasticity. To aid in resolving this issue, we used a simple snail appetitive classical conditioning paradigm in which the underlying molecular, cellular, and neural network functions can be directly linked to age-associated learning and memory performance (i.e., the Lymnaea stagnalis feeding system). Our results indicate that age does not affect the acquisition of appetitive memory but that retention and/or consolidation of long-term memory become progressively impaired with advancing age. The latter phenomenon correlates with declining electrophysiological excitability in key neurons controlling the feeding behavior. Together, these results present the Lymnaea feeding system as a powerful paradigm for investigations of cellular and molecular foundations of biological aging in the brain.

Neurogenesis in the Adult and Aging Brain

Abstract: Given that neurogenesis is regionally restricted in the adult brain, the direct contribution of changes in neurogenesis to the development of aging-related cognitive decline is likely limited, perhaps accounting for the difficulty thus far in linking the decline in neurogenesis to specific neural deficits. As investigations of the contributions of adult neurogenesis to neural function continue, however, it is reasonable to expect they will demonstrate that the aging-related loss of the plasticity afforded by the continued addition of new neurons contributes to functional decline in senescence. Moreover, the interest of experimental gerontologists in the regulation of neurogenesis in the adult and aging brain extends beyond direct roles in hippocampal and olfactory function. It is reasonable to expect that the changes in neuronal microenvironment that lead to the decline in neurogenesis in older individuals may contribute to functional changes in established neurons and glial cells as well. In addition, the ability to isolate and expand neural stem cells from healthy brains, along with a rapidly growing capacity to regulate those cells and their progeny, keeps alive a vision of using transplanted stem cells to treat neurodegenerative diseases [216–221]. Even more appealing is that every advance in understanding the regulation of neurogenesis in vivo is a step toward therapeutic manipulation of endogenous progenitors to replace lost neurons or compensate for lost function [222], whether that occurring with normal aging or as a result of neurodegenerative disease. Although neuronal turnover is reduced in every neurogenic region of the aged brain, neuronal precursor cells clearly survive, remain responsive to growth factors and other physiological stimuli (e.g., [56, 58, 72, 81, 223]), and can increase their activity in response to damage (e.g., [63, 80]). Continued exploration of the regulation of neural progenitor cells in the adult and aging brain is critical not only for understanding normal, aging-related cognitive deficits, but also for progress toward the goal of using the brain’s regenerative potential to restore function lost to injury or neurodegenerative disease.

Can Endocrine Disruptors Influence Neuroplasticity In The Aging Brain

Abstract: Only within the last two decades has the adult mammalian brain been recognized for its ability to generate new nerve cells and other neural structures and in essence to rewire itself. Although hippocampal structures have received the greatest scrutiny, other sites, including the cerebral cortex, also display this potential. Such processes remain active in the aging brain, although to a lesser degree. Two of the factors known to induce neurogenesis are environmental enrichment and physical activity. Gonadal hormones, however, also play crucial roles. Androgens and estrogens are both required for the preservation of cognitive function during aging and apparently help counteract the risk of Alzheimer's disease. One overlooked threat to hormonal adequacy that requires close examination is the abundance of environmental endocrine-disrupting chemicals that interfere with gonadal function. They come in the form of estrogenic mimics, androgen mimics, anti-estrogens, anti-androgens, and in a variety of other guises. Because our brains are in continuous transition throughout the lifespan, responding both to environmental circumstances and to changing levels of gonadal steroids, endocrine-disrupting chemicals possess the potential to impair neurogenesis, and represent a hazard for the preservation of cognitive function during the later stages of the life cycle.

Zinc dyshomeostasis, ageing and neurodegeneration: implications of A2M and inflammatory gene polymorphisms.

Abstract: Zinc maintains brain functions because involved in glutaminergic transmission, in antioxidant response and in conferring biological activity to brain enzymes and growth factors. Zinc turnover is mediated by Metallothioneins (MT) which regulate the intracellular free zinc ions [Zn](i). Alterations in zinc homeostasis are associated to various brain dysfunctions, including brain inflammatory status, but little is known about its implication in the aging brain and neurodegeneration. Literature data in experimental animals suggest that zinc dyshomeostasis may occur in aging associated to a decline in brain functions. One of the causes may be an altered homeostasis of MT and other zinc-binding proteins, such as alpha2 macroglobulin (A2M), which are of protection against stress and inflammation during young/adult age but turn into being harmful in aging. In fact, despite total brain zinc content is unchanged in the brain of aged animals, with respect to the young/adult, the activity of some zinc dependent enzymes is impaired and large amount of zinc has been found in the core of Alzheimer's disease senile plaques. The role played by MT and A2M is reported in ageing and Alzheimer's disease and on some polymorphisms of A2M and inflammatory genes (cytokines and their receptors) because some of them may be affected by zinc, via MT homeostasis.

RNAi -induced silencing of the plasma membrane Ca2+ -ATPase 2 in neuronal cells : effects on Ca2+ homeostasis and cell viability

Abstract: Intraneuronal calcium ([Ca2+]i) regulation is altered in aging brain, possibly because of the changes in critical Ca2+ transporters We previously reported that the levels of the plasma membrane Ca2+-ATPase (PMCA) and the Vmax for enzyme activity are significantly reduced in synaptic membranes in aging rat brain The goal of these studies was to use RNAi techniques to suppress expression of a major neuronal isoform, PMCA2, in neurons in culture to determine the potential functional consequences of a decrease in PMCA activity Embryonic rat brain neurons and SH-SY5Y neuroblastoma cells were transfected with in vitro– transcribed short interfering RNA or a short hairpin RNA expressing vector, respectively, leading to 80% suppression of PMCA2 expression within 48 h Fluorescence ratio imaging of free [Ca2+]i revealed that primary neurons with reduced PMCA2 expression had higher basal [Ca2+]i, slower recovery from KCl-induced Ca2+ transients, and incomplete return to pre-stimulation Ca2+ levels Primary neurons and SH-SY5Y cells with PMCA2 suppression both exhibited significantly greater vulnerability to the toxicity of various stresses Our results indicate that a loss of PMCA such as occurs in aging brain likely leads to subtle disruptions in normal Ca2+ signaling and enhanced susceptibility to stresses that can alter the regulation of Ca2+ homeostasis

Contribution of glutamatergic signaling to nitrosative stress-induced protein misfolding in normal brain aging and neurodegenerative diseases.

Abstract: Glutamatergic hyperactivity, associated with Ca2+ influx and consequent production of nitric oxide (NO), is potentially involved in both normal brain aging and age-related neurodegenerative disorders. Many neurodegenerative diseases are characterized by conformational changes in proteins that result in their misfolding and aggregation. Normal protein degradation by the ubiquitin-proteasome system can prevent accumulation of aberrantly folded proteins. Our recent studies have linked nitrosative stress to protein misfolding and neuronal cell death. In particular, molecular chaperones - such as protein disulfide isomerase, glucose regulated protein 78, and heat shock proteins - can provide neuroprotection from misfolded proteins by facilitating proper folding and thus preventing aggregation. Here, we present evidence for the hypothesis that NO contributes to normal brain aging and degenerative conditions by S-nitrosylating specific chaperones that would otherwise prevent accumulation of misfolded proteins.

Role of calcium in normal aging and neurodegeneration.

Abstract: The calcium hypothesis of aging was born in the 1980s whencalcium signalling systems in neural cells were first characterizedin detail. Conceptually, the calcium hypothesis links relativelyearly and minor defects in calcium homeostasis with long-termdetrimental effects of this dysregulation on brain cells, whichin the course of decades affects synaptic transmission andintegrative functions of neural cells, eventually determiningage-associated cognitive decline.This Special Issue represents a collection of papers that over-view various aspects of the calcium hypothesis of aging, withparticular focus on the aging brain. It begins with a generalintroduction to the calcium hypothesis of aging in its presentstate (E. C. Toescu & A. Verkhratsky). It follows with a detailedaccount of morphological changes in the aged brain (D. Dickstein

Imaging and the aging brain

Abstract: Foreword: Mony J. De Leon. Part I: In Vivo Imaging of Molecules, Cells, and Networks in Aging and Animal Models of Alzheimer's:. 1. Making New Memories: The Role of the Hippocampus in New Associative Learning: Wendy A. Suzuki. 2. Anatomical and Functional Phenotyping of Mice Models of Alzheimer's Disease by MR Microscopy: Helene Benveniste, Yu Ma, Jasbeer Dhawan, Andrew Gifford, S. David Smith, Igor Feinstein, Congwu Du, Samuel C. Grant, and Patrick R. Hof. 3. Various Dendritic Abnormalities Are Associated with Fibrillar Amyloid Deposits in Alzheimer's Disease: Jaime Grutzendler, Kathryn Helmin, Julia Tsai, and Wen-Biao Gan. 4. Two-Photon Imaging of Astrocytic Ca2+ Signaling and the Microvasculature in Experimental Mice Models of Alzheimer's Disease: Takahiro Takano, Xiaoning Han, Rashid Deane, Berislav Zlokovic, and Maiken Nedergaard. 5. Synaptic and Mitochondrial Morphometry Provides Structural Correlates of Successful Brain Aging: Carlo Bertoni-Freddari, Patrizia Fattoretti, Belinda Giorgetti, Yessica Grossi, Marta Balietti, Tiziana Casoli, Giuseppina Di Stefano, and Gemma Perretta. 6. Impaired Recognition Memory and Decreased Prefrontal Cortex Spine Density in Aged Female Rats: Maureen Wallace, Maya Frankfurt, Adolfo Arellanos, Tomoko Inagaki, and Victoria Luine. 7. Alzheimer Amyloid beta-Peptide A-beta25 35 Blocks Adenylate Cyclase-Mediated Forms of Hippocampal Long-Term Potentiation: Blaine E. Bisel, Kristen M. Henkins, and Karen D. Parfitt. 8. Age-Related Changes in Neuronal Susceptibility to Damage: Comparison of the Retinal Ganglion Cells of Young and Old Mice Before and After Optic Nerve Crush: Ai Ling Wang, Ming Yuan, and Arthur H. Neufeld. Part II: In Vivo Imaging of Human Aging and the Transition to Cognitive Impairment:. 9. Top-Down Modulation and Normal Aging: Adam Gazzaley and Mark D'Esposito. 10. Brain Aging and Its Modifiers: Insights from in Vivo Neuromorphometry and Susceptibility Weighted Imaging: Naftali Raz, Karen M. Rodrigue, and E. Mark Haacke. 11. Linking Brain Imaging and Genomics in the Study of Alzheimer's Disease and Aging: Eric M. Reiman. 12. Imaging and CSF Studies in the Preclinical Diagnosis of Alzheimer's Disease: M. J. De Leon, L. Mosconi, K. Blennow, S. Desanti, R. Zinkowski, P. D. Mehta, D. Pratico, W. Tsui, L. A. Saint Louis, L. Sobanska, M. Brys, Y. Li, K. Rich, J. Rinne, and H. Rusinek. 13. Functional MRI Studies of Associative Encoding in Normal Aging, Mild Cognitive Impairment, and Alzheimer's Disease: Reisa Sperling. 14. Quantitative EEG and Electromagnetic Brain Imaging in Aging and in the Evolution of Dementia: Leslie S. Prichep. 15. [123I]5-IA-85380 SPECT Imaging of beta2-Nicotinic Acetylcholine Receptor Availability in the Aging Human Brain: Effie M. Mitsis, Kelly P. Cosgrove, Julie K. Staley, Erin B. Frohlich, Frederic Bois, Gilles D. Tamagnan, Kristina M. Estok, John P. Seibyl, and Christopher H. Van Dyck. 16. Role of Aerobic Fitness and Aging on Cerebral White Matter Integrity: Bonita L. Marks, David J. Madden, Barbara Bucur, James M. Provenzale, Leonard E. White, Roberto Cabeza, and Scott A. Huettel. 17. Age-Related Changes in Nociceptive Processing in the Human Brain: Raimi L. Quiton, Steven R. Roys, Jiachen Zhuo, Michael L. Keaser, Rao P. Gullapalli, and Joel D. Greenspan. 18. Magnetic Resonance Spectroscopy and Environmental Toxicant Exposure: Marc G. Weisskopf. Part III: Diagnostic Applications of Imaging to Alzheimer's Disease:. 19. Tracking Alzheimer's Disease: Paul M. Thompson, Kiralee M. Hayashi, Rebecca A. Dutton, Ming-Chang Chiang, Alex D. Leow, Elizabeth R. Sowell, Greig De Zubicaray, James T. Becker, Oscar L. Lopez, Howard J. Aizenstein, and Arthur W. Toga. 20. Shifting Paradigms in Dementia: Toward Stratification of Diagnosis and Treatment Using MRI: Wiesje M. Van Der Flier, Frederik Barkhof, and Philip Scheltens. 21. Imaging-Guided Microarray: Isolating Molecular Profiles That Dissociate Alzheimer's Disease from Normal Aging: Ana Carolina Pereira, William Wu, and Scott A. Small. 22. Fibrillar and Oligomeric beta-Amyloid as Distinct Local Biomarkers for Alzheimer's Disease: Michael C. Montalto, Gill Farrar, and Cristina Tan Hehir. 23. Diffusion Tensor Imaging of Normal Appearing White Matter and Its Correlation with Cognitive Functioning in Mild Cognitive Impairment and Alzheimer's Disease: Juebin Huang and Alexander P. Auchus. 24. Enhanced Ryanodine-Mediated Calcium Release in Mutant PS1-Expressing Alzheimer's Mouse Models: Grace E. Stutzmann, Ian Smith, Antonella Caccamo, Salvatore Oddo, Ian Parker, and Frank Laferla. 25. Prospects for Prediction: Ethics Analysis of Neuroimaging in Alzheimer's Disease: J. Illes, A. Rosen, M. Greicius, and E. Racine. Index of Contributors.

Brain aging research

Abstract: The last three decades produced a striking increase in investigations of the neurobiological basis of brain aging and aging-related changes in neural and cognitive function. Experimental and clinical studies of aging have become more valuable as the population, at least in industrialized countries, has become ‘greyer’. The increase in adult life expectancy that occurred in the twentieth century produced the motivation and necessity to invest resources in increasing ‘health span’ as well as lifespan, in order to maximize quality of life and minimize the financial and social burdens associated with disability in the later years of life. Specific interest in the aging nervous system is driven by recognition that increased longevity has little appeal for most people unless it is accompanied by maintenance of cognitive abilities. Indeed, surveys of older individuals routinely show that loss of mental capacity is among their greatest fear. In recent years, neuroscientists and gerontologists, with a variety of training and experimental approaches, have applied increasingly powerful quantitative methods to investigate why neural function declines with age. New animal model systems have been developed and old ones have become better characterized and standardized. The necessary and important descriptive studies that dominated the field in earlier years are increasingly supplemented by more hypothesis-driven research, resulting in sophisticated investigations and models of the mechanisms of brain aging. This review provides a selective overview of recent and current research on brain aging. The focus throughout will be on normal brain aging and the moderate cognitive changes that often accompany it, not on aging-related neurodegenerative diseases that result in dementia. To provide a context for studies of neurobiological changes in the aging brain, a brief overview of the types of cognitive changes that are commonly seen in aging humans is first provided. The remainder of the review focuses on animal studies that are progressively overcoming the unique challenges of aging research to reveal the neurobiological mechanisms of aging-related cognitive dysfunction, and suggest new targets for therapies to prevent or ameliorate cognitive decline.