《神经科学杂志》:节食可延缓老年动物行为退化

<正>中科院上海生科院神经科学研究所蔡时青研究组发现,长寿并不一定能延缓动物的行为退化。同时,节食提高老年动物的行为能力,部分是由于节食提高了五羟色胺和多巴胺功能。相关成果日前在线发表于《神经科学杂志》(The Journal of Neuroscience)。据了解,目前衰老领域的研究主要集中在寿命调节方面,科学家已发现上百个基因可调控动物寿命。行为和认知功能退化也是动物和人类衰老的重要特征,但延长寿命是否必然延缓衰老引起的行为退化是一个非常关键但尚未破解的问题。     

《神经科学杂志》:节食可延缓老年动物行为退化

<正>中科院上海生科院神经科学研究所蔡时青研究组发现,长寿并不一定能延缓动物的行为退化。同时,节食提高老年动物的行为能力,部分是由于节食提高了五羟色胺和多巴胺功能。相关成果日前在线发表于《神经科学杂志》(The Journal of Neuroscience)。据了解,目前衰老领域的研究主要集中在寿命调节方面,科学家已发现上百个基因可调控动物寿命。行为和认知功能退化也是动物和人类衰老的重要特征,但延长寿命是否必然延缓衰老引起的行为退化是一个非常关键但尚未破解的问题。     

科研快讯

《神经科学杂志》：节食可延缓老年动物行为退化 中科院上海生科院神经科学研究所蔡时青研究组发现,长寿并不一定能延缓动物的行为退化。同时,节食提高老年动物的行为能力,部分是由于节食提高了五羟色胺和多巴胺功能。相关成果日前在线发表于《神经科学杂志》     

科研快讯

《神经科学杂志》：节食可延缓老年动物行为退化 中科院上海生科院神经科学研究所蔡时青研究组发现。长寿并不一定能延缓动物的行为退化。同时,节食提高老年动物的行为能力。部分是由于节食提高了五羟色胺和多巴胺功能。相关成果日前在线发表于《神经科学杂志》（The Journal of Neuroscience）.     

衰老过程中行为和认知功能退化的调控机制研究

随着人类预期寿命延长,人口老龄化问题越来越严重.过去几十年关于衰老的研究使人们对长寿的生物学机理有了一定的认识,然而延长寿命应以保持老年个体健康的行为和认知功能为前提,近期研究显示延长寿命不一定延缓衰老过程中的行为和认知功能退化.衰老相关行为退化的调控机制目前知道的还很少,如何实现老年人口健康的衰老是现代社会极具挑战也...     

封面说明

正随着人类预期寿命延长,人口老龄化问题日益严峻。过去的研究使人们对长寿的生物学机理有了一定的认识,然而延长寿命应以保持老年个体健康的行为和认知功能为前提,近期研究显示延长寿命不一定延缓衰老过程中的行为和认知功能退化。衰老相关行为退化的调控机制目前知道的还很少,如何实现老年人口健康的衰老,提高老年人的生活质量是现代社会极具挑战也是迫切需要解决的问题。     

地下啮齿动物视觉系统的形态结构与机能进化

感觉系统的适应进化机制一直是动物行为学研究的焦点。生活在特殊环境中的动物,其感觉系统在进化过程中表现出的显著差异更是引人注目。由于适应地下黑暗生活环境,地下啮齿动物感觉系统在各个组织水平都表现出进化和退化镶嵌的形态特征,其视觉系统表现得最为突出：视觉器官退化,有关图象分析结构、由视觉诱导产生行为反应的脑区及视觉投射严重退化,有关感受光周期的“非成像” 视觉通路结构高度发达。本文综述了地下啮齿动物视觉系统的结构、功能、进化与发育等方面的研究进展,旨在阐明地下啮齿动物视觉系统的特点,有助于开展地下啮齿动物视觉系统适应进化机制的研究。     

机器学习在动物行为分析中的应用研究进展

动物行为分析是研究动物高级神经中枢功能的一项重要技术手段,动物的行为及其规律综合反映了其心理和生理状况,在实验动物学领域得到了广泛研究。近年来,行为采集手段的发展让大量行为数据得以产生,机器学习的出现大大提升了动物行为数据的处理效率。其中,监督学习可以实现对动物行为的自动识别和分类,而无监督学习则有利于发现人眼所观测不到的新行为或异常行为,探索行为结构。本文对机器学习方法在动物行为分析中的应用进行了阐述,为后期的研究工作和方向提供参考。     

VBA开发动物行为实时记录系统及实例

对动物行为进行实时记录是行为学研究的一项重要工作。传统的行为观察方法常常无法满足实时精确记录行为的要求 ,而一些现代的行为记录系统虽功能强大但却难以推广。作者应用VBA开发了一个简捷方便的行为实时记录系统 ,可以减少记录动物行为观察的工作量 ,降低记录动物行为的观察误差 ,保证了实验数据的可靠性。同时 ,该系统具有开放性和灵活性的特点 ,可以在不同动物行为研究中应用。     

多巴胺能神经系统对睡眠-觉醒和认知的调控作用

人的精神活动高级而又复杂,至今仍是未解之谜。目前研究认为多巴胺作为脑内重要神经递质,参与调节人的精神活动和运动功能,尤其在睡眠的主动性神经调节过程,以及学习记忆等认知功能的神经环路中,多巴胺都发挥着不可替代的作用。本文将通过对多巴胺神经系统,睡眠,认知功能的概述,以及通过对多巴胺神经系统与睡眠-觉醒系统和认知功能的解剖学联系的简述,结合多巴胺神经元、多巴胺受体及多巴胺转运体等不同角度分别阐述其对睡眠-觉醒和认知功能的调控作用,以期揭开人类精神活动的产生机制的一层面纱,以及对多巴胺药物对神经退行性变疾病的治疗靶点提供一定的理论支持。     

Neuroprotective role of taurine during aging

Aging of the brain is characterized by several neurochemical modifications involving structural proteins, neurotransmitters, neuropeptides and related receptors. Alterations of neurochemical indices of synaptic function are indicators of age-related impairment of central functions, such as locomotion, memory and sensory performances. Several studies demonstrate that ionotropic GABA receptors, glutamate decarboxylase (GAD), and somatostatinergic subpopulations of GABAergic neurons are markedly decreased in experimental animal brains during aging. Additionally, levels of several neuropeptides co-expressed with GAD decrease during aging. Thus, the age-related decline in cognitive functions could be attributable, at least in part, to decrements in GABA inhibitory neurotransmission. In this study, we showed that chronic supplementation of taurine to aged mice significantly ameliorated the age-dependent decline in spatial memory acquisition and retention. We also demonstrated that concomitant with the amelioration in cognitive function, taurine caused significant alterations in the GABAergic and somatostatinergic system. These changes included (1) increased levels of the neurotransmitters GABA and glutamate, (2) increased expression of both isoforms of GAD (65 and 67) and the neuropeptide somatostatin, (3) decreased hippocampal expression of the β3 subunits of the GABA_A receptor, (4) increased expression in the number of somatostatin-positive neurons, (5) increased amplitude and duration of population spikes recorded from CA1 in response to Schaefer collateral stimulation and (6) enhanced paired pulse facilitation in the hippocampus. These specific alterations of the inhibitory system caused by taurine treatment oppose those naturally occurring in the aging brain, suggesting a protective role of taurine in this process. An increased understanding of age-related neurochemical changes in the GABAergic system will be important in elucidating the underpinnings of the functional changes of aging. Taurine supplementation might help forestall the age-related decline in cognitive functions through interaction with the GABAergic system.     

Oxidative Stress and Inflammation in Brain Aging: Nutritional Considerations

Aging can be defined as the condition where stressors are not counteracted by protective functions, leading to a dysregulation in development. These changes can be translated into decrements in neuronal functioning accompanied by behavioral declines, such as decreases in motor and cognitive performance, in both humans and animals. When coupled with genetic alterations, the ultimate expression of these changes is seen in diseases such as Alzheimer disease (AD). This association will be discussed in the last section of this chapter. In this review we will describe motor and cognitive deficits in behavior due to aging, and show how these deficits are related to increased vulnerability to oxidative stress, inflammation or signaling. Importantly, using muscarinic receptors as examples, we will also try to show that the sensitivity to these insults may be differentially expressed among neurotransmitter receptor subtypes.     

Molecular Bases of Caloric Restriction Regulation of Neuronal Synaptic Plasticity

Aging is associated with the decline of cognitive properties. This situation is magnified when neurodegenerative processes associated with aging appear in human patients. Neuronal synaptic plasticity events underlie cognitive properties in the central nervous system. Caloric restriction (CR; either a decrease in food intake or an intermittent fasting diet) can extend life span and increase disease resistance. Recent studies have shown that CR can have profound effects on brain function and vulnerability to injury and disease. Moreover, CR can stimulate the production of new neurons from stem cells (neurogenesis) and can enhance synaptic plasticity, which modulate pain sensation, enhance cognitive function, and may increase the ability of the brain to resist aging. The beneficial effects of CR appear to be the result of a cellular stress response stimulating the production of proteins that enhance neuronal plasticity and resistance to oxidative and metabolic insults; they include neurotrophic factors, neurotransmitter receptors, protein chaperones, and mitochondrial biosynthesis regulators. In this review, we will present and discuss the effect of CR in synaptic processes underlying analgesia and cognitive improvement in healthy, sick, and aging animals. We will also discuss the possible role of mitochondrial biogenesis induced by CR in regulation of neuronal synaptic plasticity.     

Hot topics in epigenetic mechanisms of aging: 2011

Aging is a complex process that results in compromised biological functions of the organism and increased susceptibility to disease and death. Although the molecular basis of aging is currently being investigated in many experimental contexts, there is no consensus theory to fully explain the aging process. Epigenetic factors, including DNA methylation, histone modifications, and microRNA expression, may play central roles in controlling changes in gene expression and genomic instability during aging. In this Hot Topic review, we first examine the mechanisms by which these epigenetic factors contribute to aging in diverse eukaryotic species including experimental models of yeasts, worms, and mammals. In a second section, we will emphasize in the mammalian epigenetic alterations and how they may affect human longevity by altering stem cell function and/or somatic cell decline. The field of aging epigenetics is ripe with potential, but is still in its infancy, as new layers of complexity are emerging in the epigenetic network. As an example, we are only beginning to understand the relevance of non-coding genome to organism aging or the existence of an epigenetic memory with transgenerational inheritance. Addressing these topics will be fundamental for exploiting epigenetics phenomena as markers of aging-related diseases or as therapeutic targets.     

Ovarian aging and menopause: current theories, hypotheses, and research models

Aging of the reproductive system has been studied in numerous vertebrate species. Although there are wide variations in reproductive strategies and hormone cycle components, many of the fundamental changes that occur during aging are similar. Evolutionary hypotheses attempt to explain why menopause occurs, whereas cellular hypotheses attempt to explain how it occurs. It is commonly believed that a disruption in the hypothalamic-pituitary-gonadal axis is responsible for the onset of menopause. Data exist to demonstrate that the first signs of menopause occur at the level of the brain or the ovary. Thus, finding an appropriate and representative animal model is especially important for the advancement of menopause research. In primates, there is a gradual decline in the function of the hypothalamic-pituitary-gonadal (HPG) axis ultimately resulting in irregularities in menstrual cycles and increasingly sporadic incidence of ovulation. Rodents also exhibit a progressive deterioration in HPG axis function; however, they also experience a period of constant estrus accompanied by intermittent ovulations, reduced progesterone levels, and elevated circulating estradiol levels. It is remarkable to observe that females of other classes also demonstrate deterioration in HPG axis function and ovarian failure. Comparisons of aging in various taxa provide insight into fundamental biological mechanisms of aging that could underlie reproductive decline.     

The role of PGC-1 coactivators in aging skeletal muscle and heart

Aging is the progressive decline in cellular, tissue, and organ function. This complex process often manifests as loss of muscular strength, cardiovascular function, and cognitive ability. Mitochondrial dysfunction and decreased mitochondrial biogenesis are believed to participate in metabolic abnormalities and loss of organ function, which will eventually contribute to aging and decreased lifespan. In this review, we discuss what is currently known about mitochondrial dysfunction in the aging skeletal muscle and heart. We focused our discussion on the role of PGC-1 coactivators in the regulation of mitochondrial biogenesis and function and possible therapeutic benefits of increased mitochondrial biogenesis in compensating for mitochondrial dysfunction and circumventing aging and aging-related diseases.     

Age-related white matter microstructural differences partly mediate age-related decline in processing speed but not cognition

Aging is associated with declining cognitive performance as well as structural changes in brain gray and white matter (WM). The WM deterioration contributes to a disconnection among distributed brain networks and may thus mediate age-related cognitive decline. The present diffusion tensor imaging (DTI) study investigated age-related differences in WM microstructure and their relation to cognition (episodic memory, visuospatial processing, fluency, and speed) in a large group of healthy subjects (n = 287) covering 6 decades of the human life span. Age related decreases in fractional anisotropy (FA) and increases in mean diffusivity (MD) were observed across the entire WM skeleton as well as in specific WM tracts, supporting the WM degeneration hypothesis. The anterior section of the corpus callosum was more susceptible to aging compared to the posterior section, lending support to the anterior-posterior gradient of WM integrity in the corpus callosum. Finally, and of critical interest, WM integrity differences were found to mediate age-related reductions in processing speed but no significant mediation was found for episodic memory, visuospatial ability, or fluency. These findings suggest that compromised WM integrity is not a major contributing factor to declining cognitive performance in normal aging. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.     

Neuronal‐specific proteasome augmentation via Prosβ5 overexpression extends lifespan and reduces age‐related cognitive decline

Cognitive function declines with age throughout the animal kingdom, and increasing evidence shows that disruption of the proteasome system contributes to this deterioration. The proteasome has important roles in multiple aspects of the nervous system, including synapse function and plasticity, as well as preventing cell death and senescence. Previous studies have shown neuronal proteasome depletion and inhibition can result in neurodegeneration and cognitive deficits, but it is unclear if this pathway is a driver of neurodegeneration and cognitive decline in aging. We report that overexpression of the proteasome β5 subunit enhances proteasome assembly and function. Significantly, we go on to show that neuronal‐specific proteasome augmentation slows age‐related declines in measures of learning, memory, and circadian rhythmicity. Surprisingly, neuronal‐specific augmentation of proteasome function also produces a robust increase of lifespan in Drosophila melanogaster. Our findings appear specific to the nervous system; ubiquitous proteasome overexpression increases oxidative stress resistance but does not impact lifespan and is detrimental to some healthspan measures. These findings demonstrate a key role of the proteasome system in brain aging.     

As time flies by: Investigating cardiac aging in the short-lived Drosophila model

Aging is associated with a decline in heart function across the tissue, cellular, and molecular levels. The risk of cardiovascular disease grows significantly over time, and as developed countries continue to see an increase in lifespan, the cost of cardiovascular healthcare for the elderly will undoubtedly rise. The molecular basis for cardiac function deterioration with age is multifaceted and not entirely clear, and there is a limit to what investigations can be performed on human subjects or mammalian models. Drosophila melanogaster has emerged as a useful model organism for studying aging in a short timeframe, benefitting from a suite of molecular and genetic tools and displaying highly conserved traits of cardiac senescence. Here, we discuss recent advances in our understanding of cardiac aging and how the fruit fly has aided in these developments.     

Joint Modeling for Cognitive Trajectory and Risk of Dementia in the Presence of Death

Summary .  Dementia is characterized by accelerated cognitive decline before and after diagnosis as compared to normal aging. It has been known that cognitive impairment occurs long before the diagnosis of dementia. For individuals who develop dementia, it is important to determine the time when the rate of cognitive decline begins to accelerate and the subsequent gap time to dementia diagnosis. For normal aging individuals, it is also useful to understand the trajectory of cognitive function until their death. A Bayesian change-point model is proposed to fit the trajectory of cognitive function for individuals who develop dementia. In real life, people in older ages are subject to two competing risks, e.g., dementia and dementia-free death. Because the majority of people do not develop dementia, a mixture model is used for survival data with competing risks, which consists of dementia onset time after the change point of cognitive function decline for demented individuals and death time for nondemented individuals. The cognitive trajectories and the survival process are modeled jointly and the parameters are estimated using the Markov chain Monte Carlo method. Using data from the Honolulu Asia Aging Study, we show the trajectories of cognitive function and the effect of education, apolipoprotein E 4 genotype, and hypertension on cognitive decline and the risk of dementia.