Effects of Noise Exposure Across the Lifespan on Balance and Stability in Older Adults

摘要 失稳和福尔斯是老年人受伤和死亡的主要危险因素。以前被忽视的， 已经证明，终生暴露于噪声会对前庭周围造成损害;尽管动物模型 和人类研究，可以提供一个机械基础连接噪声引起的前庭功能障碍， 与年龄相关的跌倒风险有限。前庭系统在头部运动的检测中起着关键作用， 相对于重力定向，并且对于正常视觉和姿势控制是必不可少的。由于其 由于耳石器官在解剖学上接近耳蜗，因此耳石器官暴露在声压下，并有噪声的风险 过度刺激，这可能导致前庭功能障碍。然而，损害可能不仅限于 耳石器官最近的研究表明，噪声过度刺激与前庭神经活动减少和丧失有关 一种特殊类型的不规则前庭传入神经，对加速度表现出增强的敏感性。 很可能这些传入神经起着重要的作用，它启动了对突然变化的姿势补偿。 由于它们生理特征和它们对次级前庭的投射， 投射到脊髓的神经元。因此，噪音的影响可能会加速与 自然老化这项提案的目的是描述与自然衰老相关的前庭功能丧失，以及如何 此外，在人的一生中，所接触的噪音累积起来，因此，我们将系统地研究 寿命期内噪声暴露对耳石和耳道结构和功能的影响（目标1）， 明确指出不规则传入损害的程度及其功能后果（目标2），并评估 噪音暴露对姿势、移动性和平衡的影响（目标3）。感觉细胞突触的变化 与前庭反射障碍和与姿势不稳定和丧失 平衡为了更好地了解这些变化在生命周期中是如何发生的，我们将评估 成年早期、中期和晚期的解剖学和功能变化。此外，功能实验将 在大鼠和人类参与者中平行进行，以最大限度地将我们的结果转化为临床。 动物和啮齿类动物的研究对我们理解噪音的影响都是非常有价值的 暴露对前庭功能的影响然而，这两种方法都有局限性，最好用一套 两个系统的互补研究。该提案描述了一个全面的、多学科的 一种方法，该方法致力于评价由于以下病史导致的福尔斯和跌倒风险增加的潜在机制： 老年人的噪音暴露。这些个体对潜在致命福尔斯跌倒的易感性强调了 需要一种系统的方法，最终可以改善训练和康复方法， 用在这个人群中。

Abstract Loss of stability and falls is a major risk factor for injury and death in older adults. Previously overlooked, lifetime noise exposure has been shown to cause damage to the vestibular periphery; although, animal models and human studies that can provide a mechanistic basis connecting noise-induced vestibular dysfunction and age-related fall risk are limited. The vestibular system plays a critical role in detection of head movements and orientation with respect to gravity and is essential for normal vision and postural control. Due to their anatomical proximity to the cochlea, the otolith organs are exposed to sound pressure and are at risk for noise overstimulation, which may contribute to vestibular dysfunction. However, damage may not be limited to the otolith organs. Recent studies have linked noise overstimulation to decreased vestibular nerve activity and loss of a specialized class of irregularly firing vestibular afferents which exhibit enhanced sensitivity to acceleration. It is likely that these afferents play an important role initiating postural compensation for abrupt changes in head or body position due to their physiological characteristics and their projection to secondary vestibular neurons that project to the spinal cord. Therefore, the effects of noise may accelerate disability associated with natural aging. The goal of this proposal is to characterize vestibular loss associated with natural aging and how it is compounded by cumulative noise exposures throughout one’s life. Thus, we will systematically investigate the effects of noise exposure across the lifespan on otolith and canal structure and function (Aim 1), specifically address the extent of irregular afferent damage and its functional consequences (Aim 2), and asses changes in posture, mobility and balance with noise exposure (Aim 3). Changes in sensory cell synapses will be correlated with vestibular reflex impairment and fall risk associated with postural instability and loss of balance. To improve our understanding of how these changes occur over the lifetime, we will assess anatomical and functional changes in early-, middle-, and late-adulthood. Further, functional experiments will be done in parallel in rats and human participants for maximal translation of our results to the clinic. Individually, both animal and rodent studies have proven invaluable to our understanding of the effects of noise exposure on vestibular function. However, both have limitations that can be best addressed with a set of complimentary studies in the two systems. This proposal describes a comprehensive, multidisciplinary approach that strives to evaluate the underlying mechanisms in increased falls and fall risk due to a history of noise exposure in older adults. The susceptibility of these individuals to potentially fatal falls underscores the need for a systematic approach, that can eventually result in improved training and rehabilitation methods to be used with this population.