Age-related changes in skeletal muscle and lower urinary tract symptoms in older adults

项目摘要/摘要 由于目前对以下问题缺乏了解，存在根本的知识差距和错失的机会 与年龄相关的危险因素之间的关系，如全身骨骼肌和骨盆骨骼肌的丧失 老年女性和男性的功能和下尿路症状(LUTS)。LUT与以下各项相关联 功能受损，生活质量差，摔倒、骨折和死亡的风险增加。这个 目前对尿路病理的狭隘关注导致了对导致这些疾病的原因的了解很少 症状和相应的有效干预措施很少。一种新的关注老龄化的LUTS范式 病理生理学可以通过定义可改变的LUTS风险因素来导致治疗LUTS的新干预措施，例如 随着年龄的增长，肌肉健康的变化，以及衰老症状之间的共同机制。 我的目标是建立一个流行病学的支柱，通过以下方式了解与年龄相关的LUTS风险因素 利用高质量的现有数据，为年龄定义新的和可修改的风险因素和机制- 相关的LUT，并领导后续的翻译工作，以针对老年人的这些风险因素和机制 成年人。此应用程序的目标是评估以下多个测量之间的纵向关联 骨骼肌和LUT。我的假设是骨骼肌中与年龄相关的变化-在系统中 (力量和体能)、器官(肌肉质量/体积)和细胞(线粒体生物能量学) 水平-与LUTS的严重程度相关，与年龄和混杂因素无关。 这一假设将通过有效地使用来自前瞻性队列研究的数据进行检验 和老龄化“(Somma)以追求以下具体目标：目标1)确定基线和纵向 肌肉功能(力量、力量)和体能(行走速度)的变化与 LUTS严重程度的变化；目标2)确定肌肉质量和肌肉质量的基线和纵向变化 全身和盆底肌肉体积和形状的基线测量与 LUTS严重性；和目标3)确定骨骼肌线粒体功能的基线测量 与LUTS严重程度的变化相关。该项目具有创新性，因为它利用了快速发展的 老年科学领域，以改善现有的以泌尿生殖系统为重点的LUTS病理生理学范例的不足。 这项拟议的研究具有重要意义，因为它将产生与年龄相关的LUTS病理生理学范式 这将通过以下方式改善对患有下尿路感染的老年人的护理：1)确定与年龄相关的下尿路感染的生物标志物；2) 根据新的LUTS表型进行分层，提高现有疗法的收益：风险比；3) 辨别全球肌肉和盆底肌肉变化在LUTS发生中的作用；4) 促进针对与年龄相关的LUTS机制的新治疗方法的开发；并最终5) 预防LUTS并发症(如虚弱、行动不便、跌倒和生活质量差) 由LUTS引起的或间接由共同的可修改因素引起的，LUTS是其早期标志。

PROJECT SUMMARY/ABSTRACT There is a fundamental knowledge gap and missed opportunities due to the current lack of understanding of the relationship between age-related risk factors, such as loss of both global and pelvic skeletal muscle function, and lower urinary tract symptoms (LUTS) among older women and men. LUTS are associated with functional impairment and poor quality of life and are at increased risk of falls, fractures, and mortality. The current narrow focus on urinary tract pathology has led to minimal understanding of what causes these symptoms and correspondingly few effective interventions. A new aging-focused paradigm of LUTS pathophysiology could lead to novel interventions to treat LUTs by defining modifiable LUTS risk factors, such as age-related changes in muscle health, and mechanisms shared across syndromes of aging. My goals are to build an epidemiologic backbone for understanding age-related LUTS risk factors by leveraging high-quality existing data, defining novel and modifiable risk factors and mechanisms for age- related LUTS, and to lead subsequent translational efforts to target these risk factors and mechanisms in older adults. The objective of this application is to evaluate longitudinal associations between multiple measures of skeletal muscle and LUTS. My hypothesis is that age-related changes in skeletal muscle – at the system (strength and physical performance), organ (muscle mass/volume), and cellular (mitochondrial bioenergetics) level – are associated with LUTS severity, independent of chronological age and confounding factors. This hypothesis will be tested by efficiently using data from the prospective cohort “Study of Muscle Mobility and Aging” (SOMMA) to pursue the following specific aims: Aim 1) Determine how baseline and longitudinal changes in muscle function (strength, power) and physical performance (walking speed) are associated with change in LUTS severity; Aim 2) Determine how baseline and longitudinal changes in muscle mass and baseline measures of both total body and pelvic floor muscle volume and shape are associated with change in LUTS severity; and Aim 3) Determine how baseline measures of skeletal muscle mitochondrial function are associated with change in LUTS severity. This project is innovative because it leverages the rapidly evolving field of geroscience to improve the inadequate existing urogenital-focused paradigm of LUTS pathophysiology. The proposed research is significant because it will produce a paradigm of age-related LUTS pathophysiology that will result in improved care for older adults with LUTS by 1) identifying biomarkers of age-related LUTS; 2) improving the benefit:risk ratio for existing therapies by stratifying based on novel LUTS phenotypes; 3) distinguishing the role of changes in global versus pelvic floor muscles in the development of LUTS; 4) facilitating the development of new treatments that target age-related LUTS mechanisms; and ultimately 5) preventing LUTS complications (e.g., frailty, impaired mobility, falls, and poor quality of life) that may be directly caused by LUTS or indirectly caused by shared modifiable factors for which LUTS is an early marker.