Abstract Older adults struggle to engage in health enhancing physical activity (PA) and spend up to 11 hours a day sitting. Older women, in particular, are at increased risk of chronic disease and disability, and use a high proportion of healthcare resources. Improving both these behaviors has promise for improving several salient aging outcomes, but evidence to inform guidelines on how best to interrupt long periods of sedentary behavior (SB) are lacking. Few laboratory-based trials have included adults over 70 years old, have focused on PA to interrupt SB, and have not tested standing breaks that might be acceptable to older adults. A recent review showed that in the real world, traditional PA interventions do not meaningfully impact SB. In contrast, interventions that focus on standing can reduce SB, up to 2 hours per day. Epidemiological studies have shown associations between self-reported SB and increased risks of death and metabolic outcomes, but very few prospective studies have employed objective measures of SB. Although accelerometer measures can indicate the intensity of movement or lack of it, traditional cutpoints do not accurately classify behaviors such as sitting, standing or walking. While pilot intervention studies, using thigh worn inclinometers, have demonstrated that SB can be greatly reduced, there are no RCTs in older adults with health outcomes. There is much room for improvement in our understanding of SB and healthy aging. The National Institute on Aging conducted a summer workshop series to address this issue in 2013. We have therefore designed a Program project ? Sedentary Time and Aging Research (STAR) ? to provide more rigorous and comprehensive evidence on how to interrupt sitting time and the consequences for healthy aging. In particular, we are proposing a paradigm shift away from energy expenditure as the primary mechanism for health outcomes to investigating behaviors such as brief sit-to-stand transitions that expend little energy but engage muscles, improve postural blood flow, and may impact physical functioning in older adults. Further, we will study a broader range of outcomes than investigated to date, including targeted novel mechanisms important for healthy aging. The STAR program will include 3 Projects and 2 Cores for study of postmenopausal women at risk for chronic disease. STAR includes 2 randomized trials, in the laboratory (N=86) and in the real world (N=592), with focus on optimizing new computational techniques to apply to existing prospective accelerometer data (n>6000). All projects will investigate the consequences of extended sitting, standing, brief sit-to-stand transitions and PA breaks on mechanisms of healthy aging including glucose regulation, endothelial functioning, and mitochondrial functioning. We will also investigate physical functioning, blood pressure and in Project 3, 5-7 year mortality risk. All Projects will compare effects across age groups. STAR will provide a comprehensive evidence base that can inform public health guidelines on SB and aging. We will coordinate our efforts with a new American Heart Association Center on SB and Latinas.