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

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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.