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

老年人骨骼肌和下尿路症状与年龄相关的变化

• 批准号: 10493395
• 负责人: Scott Ryan Bauer
• 金额: $ 24.05万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10493395
• 关键词: Address; Adult; Age; Aging; Ancillary Study; Bioenergetics; Biological; Biological Markers; Bladder; Caring; Chronology; Clinical; Creatine; Data; Denervation; Development; Diagnosis; Elderly; Epidemiology; Etiology; Female; Fracture; Frail Elderly; Frequencies; Functional disorder; Funding; Gait speed; Genitourinary system; Geroscience; Goals; Gold; Hand Strength; Health; Impairment; Incontinence; Intervention; Knowledge; Lead; Leg; Measurement; Measures; Mitochondria; Muscle; Muscle Mitochondria; Muscle function; National Institute of Diabetes and Digestive and Kidney Diseases; Nocturia; Organ; Outcome; Pathology; Pelvic Floor Muscle; Pelvic floor structure; Pelvis; Personal Satisfaction; Phenotype; Physical Function; Physical Performance; Physical assessment; Practice Guidelines; Process; Prospective cohort; Prospective cohort study; Prostate; Public Health; Quality of life; Research; Respiration; Risk; Risk Factors; Role; Science; Severities; Shapes; Skeletal Muscle; Stream; Symptoms; Syndrome; System; Testing; Thigh structure; Time; United States National Institutes of Health; Urinary tract; Urine; Urodynamics; Vertebral column; Woman; accurate diagnosis; age related; associated symptom; base; cohort; effective intervention; epidemiology study; experience; fall risk; falls; frailty; functional disability; health related quality of life; improved; individualized medicine; innovation; levator ani muscle; lower urinary tract symptoms; male; men; modifiable risk; mortality; multiple chronic conditions; muscle aging; muscle form; novel; older men; older women; oxidative damage; prevent; quadriceps muscle; reduced muscle mass; respiratory; risk benefit ratio; sex; tool; urogenital tract; walking speed

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.

项目概要/摘要 由于目前缺乏了解，存在基本知识差距并错失了机会 与年龄相关的危险因素之间的关系，例如整体骨骼肌和盆腔骨骼肌的丧失 老年女性和男性的功能和下尿路症状（LUTS）。 LUTS 与 功能障碍和生活质量差，跌倒、骨折和死亡的风险增加。这 目前对泌尿道病理学的狭隘关注导致人们对导致这些疾病的原因了解甚少。 症状和相应的有效干预措施很少。 LUTS 的新的关注衰老的范例 病理生理学可以通过定义可改变的 LUTS 危险因素来治疗 LUT 的新干预措施，例如 与年龄相关的肌肉健康变化以及衰老综合症共有的机制。 我的目标是建立一个流行病学支柱来了解与年龄相关的 LUTS 风险因素 利用高质量的现有数据，定义新颖且可改变的风险因素和年龄机制 相关的 LUTS，并领导后续的转化工作，以针对老年患者的这些风险因素和机制 成年人。此应用程序的目的是评估多个指标之间的纵向关联 骨骼肌和 LUTS。我的假设是骨骼肌的年龄相关变化 - 在系统中 （力量和身体表现）、器官（肌肉质量/体积）和细胞（线粒体生物能量学） 水平——与 LUTS 严重程度相关，与实际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“肌肉活动性研究”的数据来检验 和老龄化”（SOMMA），以追求以下具体目标： 目标 1）确定基线和纵向如何 肌肉功能（力量、功率）和身体表现（步行速度）的变化与 LUTS 严重程度发生变化；目标 2) 确定肌肉质量的基线和纵向变化以及 全身和盆底肌肉体积和形状的基线测量与 LUTS 严重程度；目标 3) 确定骨骼肌线粒体功能的基线测量结果如何 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技术 老年科学领域的研究旨在改善现有以泌尿生殖系统为中心的 LUTS 病理生理学范式的不足。 这项研究意义重大，因为它将产生与年龄相关的 LUTS 病理生理学范例 这将通过以下方式改善对患有 LUTS 的老年人的护理： 1) 识别与年龄相关的 LUTS 生物标志物； 2） 根据新的 LUTS 表型进行分层，提高现有疗法的获益：风险比； 3） 区分整体肌肉变化与盆底肌肉变化在 LUTS 发展中的作用； 4） 促进针对年龄相关 LUTS 机制的新疗法的开发；最后 5) 预防可能直接导致 LUTS 并发症（例如虚弱、活动能力受损、跌倒和生活质量差） 由 LUTS 引起或由共同的可改变因素间接引起（LUTS 是其早期标志）。