DESCRIPTION (provided by applicant): Sarcopenia, the age-related loss of skeletal muscle mass, contributes to impaired mobility, frailty and disability. However, there is a mismatch between the loss in muscle mass and loss in muscle strength, suggesting that muscle quality is impaired with aging. Infiltration of fat into skeletal muscle (myosteatosis) affects muscle quality and may be related to impaired mobility and disability. Muscle quantity and muscle quality are potentially early modifiable factors in the development of frailty. The goal of this proposal is to examine whether infiltration of fat into skeletal muscle, assessed by peripheral quantitative computed tomography, independently and interactively predicts decline in muscle strength, physical performance, frailty, disability and death in a prospective cohort of 1,172 community dwelling men aged 65 years and older. Furthermore, we hypothesize that interventions that improve both muscle mass and quality will prevent weakness and disability. Thus, our second aim is to study whether a low-impact, nonpharmacologic device providing low magnitude mechanical stimulation to the whole body improves muscle strength in low functioning adults. This proposal will also explore whether low magnitude mechanical increases muscle mass and decrease intermuscular fat. Subjects will be recruited from local assisted living communities, which provide congregate housing and social events for many older adults. We hypothesize that low magnitude mechanical stimulation will help combat sarcopenia and loss of independence among frail older adults who are at the highest risk of adverse outcomes. The candidate for this mentored Patient-Oriented Career Development Award aims to complement her previous training in geriatrics and epidemiology with additional expertise in muscle physiology, body composition imaging methodology, and interventional clinical research. Columbia University has committed abundant resource to support this proposal including the use of bionutrition, biomarkers laboratory in the NIH CTSA-funded Irving Institute. A multidisciplinary mentorship team comprised of experts in frailty, body composition, intermuscular fat and clinical trial design in the elderly supports the proposal. The proposed studies should provide novel information about the importance of intermuscular fat in the development of disability, and could lead to new strategies for the treatment and prevention of sarcopenia.

Frailty is a geriatric syndrome that identifies vulnerable adults at increased risk for adverse outcomes. Central to the multisystem dysregulation is sarcopenia and age-related loss in muscle strength. The economic impact of sarcopenia and its detrimental consequences are immense. Pharmacologic and nonpharmacologic treatment options are badly needed. Resistance training improves multiple outcomes, however, many older adults are unable to participate in high-intensity exercise programs. Low magnitude mechanical stimulation is an exciting and novel low impact intervention to combat the loss of muscle strength in older adults. This may have a large public health impact in preventing disability.