Sex-specific determinants of muscle quality in older adults

Project Summary / Abstract Sarcopenia, the age-related loss of physical function, is caused by loss of muscle mass and/or muscle quality (MQ: function relative to size) and accounts for >$40 billion in annual US healthcare costs. While sarcopenia is more prevalent in males it’s more strongly related to adverse health outcomes in females. Despite this, sex- specific sarcopenia etiology is poorly understood, and interventions to prevent or treat sarcopenia are not sex- specific. Previous reports have noted that males experience greater reductions in muscle mass and increases in muscle adiposity than females while female experience greater neurological impairment and muscle stiffening than males. However, no studies have directly compared the sex-specific relationships between these proposed determinants of MQ and directly measured MQ (force per volume) and detailed exploration of the sex-specific excitatory and inhibitory pathways contributing to neurological impairment is needed. This knowledge is essential for creating sex-specific sarcopenia diagnostic criteria and identifying sex-specific therapeutic targets to improve MQ. As an accomplished sports scientist whose previous work has focused on improving MQ in elite athletes but has spent the last 3 years transitioning this work to older adults, the goal of this career development award is to provide me the training, research experience, and preliminary data that is necessary for me to establish myself as a geriatric researcher specializing in targeted interventions to improve muscle quality in older adults. This will be accomplished by completing a training plan that develops my skills and knowledge in precision gerontology and components of MQ present that are unique to older adults (corticospinal impairment, muscle fat infiltration, and muscle stiffening). These skills will then be put into practice by completing two supplemental studies and a primary research study which explore the sex-specific determinants of MQ. The supplemental studies are examinations of ~31,000 older adults in the UK Biobank Imaging Study to determine sex-specific relationships between muscle fat infiltration, physical activity patterns, and diet quality. In the primary study, I will directly measure quadriceps MQ, neurological impairment (central activation ratio), muscle adiposity, and muscle stiffness in 60 older (≥65 yr) age-matched males (n=30) and females (n=30) determine if the determinants of MQ differ between sexes. The function of four distinct corticospinal excitation / inhibition pathways will also be compared between sexes, to determine if there are sex-specific pathways which contribute to neurological impairment of muscle. Through these studies sex- specific therapeutic targets to improve MQ will be identified and a subsequent R01 application will test the sex- specific effects of the current standard sarcopenia treatment, resistance training, on these therapeutic targets.