PDF(Pubmed)
Abstract：
Early adversity is an important risk factor that influences brain aging. Diverse animal models of early adversity, including gestational stress and postnatal paradigms disrupting dam-pup interactions evoke not only persistent neuroendocrine dysfunction and anxio-depressive behaviors, but also perturb the trajectory of healthy brain aging. The process of brain aging is thought to involve hallmark features such as mitochondrial dysfunction and oxidative stress, evoking impairments in neuronal bioenergetics. Furthermore, brain aging is associated with disrupted proteostasis, progressively defective epigenetic and DNA repair mechanisms, the build-up of neuroinflammatory states, thus cumulatively driving cellular senescence, neuronal and cognitive decline. Early adversity is hypothesized to evoke an \"allostatic load\" via an influence on several of the key physiological processes that define the trajectory of healthy brain aging. In this review we discuss the evidence that animal models of early adversity impinge on fundamental mechanisms of brain aging, setting up a substratum that can accelerate and compromise the time-line and nature of brain aging, and increase risk for aging-associated neuropathologies.
摘要：
早期逆境是影响大脑衰老的重要危险因素。早期逆境的各种动物模型，包括妊娠压力和产后范式破坏dam-pup相互作用不仅引起持续的神经内分泌功能障碍和焦虑抑郁行为，但也扰乱了健康大脑衰老的轨迹。大脑衰老的过程被认为涉及线粒体功能障碍和氧化应激等标志性特征，引起神经元生物能学的损伤。此外，大脑衰老与蛋白质紊乱有关，渐进缺陷的表观遗传和DNA修复机制，神经炎症状态的积累，因此累积驱动细胞衰老，神经元和认知能力下降。据推测，早期逆境会通过对定义健康大脑衰老轨迹的几个关键生理过程的影响来引起“同种异体负荷”。在这篇综述中，我们讨论了早期逆境动物模型影响大脑衰老的基本机制的证据。建立一个可以加速和损害大脑衰老的时间线和性质的基础，并增加与衰老相关的神经病变的风险。
