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: 10646356
• 负责人: Scott Ryan Bauer
• 金额: $ 24.23万
• 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/10646356
• 关键词: Address; Adult; Age; Aging; Ancillary Study; Bioenergetics; Biological; Biological Markers; Bladder; Caring; Cessation of life; Chronology; Clinical; Creatine; Data; Denervation; Development; Diagnosis; Elderly; Epidemiology; Etiology; Female; Fracture; Frail Elderly; Frequencies; Functional disorder; Funding; Gait speed; Genitourinary system; Geroscience; Goals; 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; 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; biomarker identification; cohort; effective intervention; epidemiology study; experience; fall risk; falls; frailty; functional disability; health related quality of life; human old age (65+); improved; individualized medicine; innovation; levator ani muscle; lower urinary tract symptoms; male; men; modifiable risk; mortality; multiple chronic conditions; muscle form; novel; older men; older women; oxidative damage; prevent; prostate enlargement; 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.

项目摘要/摘要 由于目前对 与年龄相关的危险因素之间的关系，例如全球和骨盆骨骼肌的丧失 老年男女的功能和较低的尿路症状（LUTS）。 LUTS与 功能障碍和生活质量差，跌倒，断裂和死亡率的风险增加。 当前对尿路病理学的关注狭窄导致对这些导致这些的原因最少了解 症状和相应的有效干预措施。一个新的以衰老为中心的LUTS范式 病理生理可能会通过定义可修改的LUTS风险因素来导致新的干预措施来治疗LUTS，例如 随着年龄相关的肌肉健康的变化以及跨衰老综合征共享的机制。 我的目标是建立一个流行病学主链，以了解与年龄相关的LUTS风险因素 利用高质量的现有数据，定义新颖和可修改的风险因素和机制的机制 相关的LUT，并领导随后的翻译工作，以针对这些危险因素和机制 成年人。该应用的目的是评估多种测量的纵向关联 骨骼肌肉和LUTS。我的假设是与年龄相关的骨骼肌变化 - 在系统上 （力量和身体性能），器官（肌肉质量/体积）和细胞（线粒体生物能学） 水平 - 与LUTS严重程度有关，与年龄和混杂因素无关。 该假设将通过有效使用前瞻性队列的数据进行测试。 和老化”（SOMMA）追求以下特定目的：目标1）确定基线和纵向 肌肉功能（力量，力量）和身体表现（步行速度）的变化与 变化LUTS的严重程度；目标2）确定肌肉质量的基线和纵向变化 总体和骨盆底肌肉体积和形状的基线测量都与变化有关 LUTS严重程度；目标3）确定骨骼肌线粒体功能的基线测量如何 与LUTS严重程度的变化有关。该项目具有创新性，因为它利用了快速发展的 GEROSCIENCE领域，以改善LUTS病理生理学的现有以泌尿生殖器为中心的范式不足。 拟议的研究很重要，因为它将产生与年龄相关的LUTS病理生理学范式 这将导致对LUTS的老年人的护理改善1）确定与年龄相关的LUTS的生物标志物； 2） 通过基于新颖的LUTS表型进行分层，改善现有疗法的风险比率：风险比； 3） 区分全球与骨盆底肌肉中变化在LUTS发展中的作用； 4） 促进针对年龄相关的LUT机制的新疗法的发展；最终5） 防止可能直接直接 由LUTS引起或间接由LUTS的共同修改因素引起的是早期标记。

项目成果

Interpreting Geroscience-Guided Biomarker Studies.

• DOI: 10.1001/jamainternmed.2021.7812
• 发表时间: 2022-03-01
• 期刊: JAMA internal medicine
• 影响因子: 39
• 作者: Bauer SR;Newman JC
• 通讯作者: Newman JC

Perceptions of Older Men Using a Mobile Health App to Monitor Lower Urinary Tract Symptoms and Tamsulosin Side Effects: Mixed Methods Study.

• DOI: 10.2196/30767
• 发表时间: 2021-12-24
• 期刊: JMIR human factors
• 影响因子: 2.7
• 作者: Wang EY;Breyer BN;Lee AW;Rios N;Oni-Orisan A;Steinman MA;Sim I;Kenfield SA;Bauer SR
• 通讯作者: Bauer SR