Comparative age-related dynamics of primate brain epigenetics

我们的物种与其他灵长类动物和哺乳动物的区别在于我们的大大脑和令人印象深刻的认知能力。通过发育延长大脑生长，沿着特别长的寿命，对人类认知的出现至关重要，但也可能导致更容易患上精神病和与衰老有关的神经退行性疾病，如阿尔茨海默病。该项目将描述人类和其他灵长类动物大脑在成年期的分子变化，以确定区分人类大脑发育和衰老模式的特征。该项目的结果将有助于确定人类神经生物学所特有的动态寿命变化的遗传机制，并可能提高我们对常见医疗条件的理解。该项目将涉及指导和培养不同职业阶段（博士后、研究生、本科生）的受训人员的分析技能，并通过可获得的教育方案向公众传播这项研究的结果。甲基化的变化在发育和衰老中很重要，甲基化的可塑性似乎在大脑中起着关键作用，有助于形成神经元连接等过程。先前的研究已经确定了灵长类物种之间大脑甲基化模式的差异，研究人员先前的工作表明，随着年龄的增长，作用于神经系统的基因会发生甲基化的改变。该项目将专门研究大脑四个区域的DNA甲基化。这项工作将建立在现有研究的基础上，采用比较方法来确定包括人类在内的四种灵长类动物成年后几个不同大脑区域甲基化变化轨迹的差异。识别灵长类动物大脑中与年龄相关的变化的差异可以帮助我们了解区分人类大脑的特征的起源，包括神经生物学衰老的各个方面。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。

Our species is distinguished from other primates and mammals by our large brains and impressive cognitive abilities. Prolonged brain growth through development, along with a particularly long life, are essential to the emergence of human cognition, but may also lead to greater susceptibility to psychiatric and aging-related neurodegenerative disorders, like Alzheimer's disease. This project will characterize molecular changes in the brains of humans and other primates across the adult lifespan to identify features that distinguish the human pattern of brain development and aging. The results of this project will help pinpoint the genetic mechanisms underlying dynamic lifespan changes that are unique to human neurobiology and may improve our understanding of common medical conditions. The project will involve mentoring and building the analytical skills of trainees at different career stages (postdoctoral, graduate, undergraduate), and communicating results of this study to members of the public through accessible educational programming.The genetic and physiological basis of human brain development and aging are not fully understood. Changes in methylation are important in development and aging, and plasticity of methylation appears to play a key role in the brain, contributing to processes like the formation of neuronal connections. Previous studies have identified differences in brain methylation patterns among primate species, and the investigators' prior work suggests that genes acting in the nervous system undergo alterations in methylation with advancing age. This project will specifically investigate DNA methylation in four brain regions. The work will build on existing research by taking a comparative approach to identify differences in the trajectories of methylation change in several distinct brain regions across adulthood among four primate species, including humans. Identifying differences among primate brains in age-related change could help us understand the origins of traits distinguishing human brains, including aspects of neurobiological aging.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.