Multimodal Diagnostic Approaches to Advance Precision Medicine in Sarcopenia and Frailty

Abstract

Sarcopenia, defined as the loss of muscle mass, strength, and function with aging, is a geriatric syndrome with important implications for patients and healthcare systems. Sarcopenia increases the risk of clinical decompensation when faced with physiological stressors and increases vulnerability, termed frailty. Sarcopenia develops due to inflammatory, hormonal, and myocellular changes in response to physiological and pathological aging, which promote progressive gains in fat mass and loss of lean mass and muscle strength. Progression of these pathophysiological changes can lead to sarcopenic obesity and physical frailty. These syndromes independently increase the risk of adverse patient outcomes including hospitalizations, long-term care placement, mortality, and decreased quality of life. This risk increases substantially when these syndromes co-exist. While there is evidence suggesting that the progression of sarcopenia, sarcopenic obesity, and frailty can be slowed or reversed, the adoption of broad-based screening or interventions has been slow to implement. Factors contributing to slow implementation include the lack of cost-effective, timely bedside diagnostics and interventions that target fundamental biological processes. This paper describes how clinical, radiographic, and biological data can be used to evaluate older adults with sarcopenia and sarcopenic obesity and to further the understanding of the mechanisms leading to declines in physical function and frailty.

Keywords: intramuscular fat; precision medicine; sarcopenia; sarcopenic obesity.

Figure 1

Geroscience conceptual model. Proposed pathways of exploration using translational geroscience (e.g., biological pathways) and clinical geriatrics (e.g., functional assessments and imaging) to identify sarcopenic obesity and physical frailty and develop targeted interventions for mitigation.

Figure 2

A proposed model of mechanisms leading to sarcopenic obesity. The proposed interplay between adipose and muscle tissue, which is believed to contribute to the development of sarcopenic obesity, is shown. The black lines are stimulatory, while red lines with flat ends indicate inhibition. IGF1, insulin-like growth factor 1; TNF, tumor necrosis factor [10].

Figure 3

Multi-scale biomechanics and gait performance. Schematic illustrates the musculoskeletal cascade from the accumulation of intramuscular fat to reduced gait performance among older adults. This is also simultaneously emphasized, and discussed in the narrative: (A) the need for quantitative biomechanics to objectively diagnose and monitor the salient features of gait quality, including step length, width, and frequency, ground reaction forces, joint mechanics and energetics, and patterns of muscular recruitment in people with sarcopenic obesity, and (B) the evolution and widespread adoption of wearable sensors that continue to break down barriers to clinical translation.