ABSTRACT There is emerging evidence that cancer and its treatments may accelerate the normal aging process, increasing the magnitude and rate of decline in functional capacity. This accelerated aging process is hypothesized to hasten the occurrence of common adverse age-related outcomes in cancer survivors, including loss of muscle mass and decrease in physical function. However, there is no data describing age-related loss of muscle mass and its relation to physical function in the long-term in cancer survivors. This project will directly address three key methodological challenges in research on cancer survivorship: 1) obtaining accurate measures of skeletal muscle mass in large population-based cohorts of community dwelling older adults, 2) disentangling the effect of age versus cancer on the relationship between muscle mass, physical function (gait speed, balance, strength), and functional decline, and 3) the large sample size required to understand predictors of low muscle mass using big data (machine learning) approaches. The D3-creatine dilution method (D3Cr) will be used to obtain a direct measure of muscle mass remotely, using a protocol that has been previously validated in clinical and epidemiologic research. This study will measure D3Cr muscle mass in 6614 participants (3044 cancer survivors and 3570 cancer-free controls) in the Women’s Health Initiative (WHI), a large prospective cohort study (n=161,808) of postmenopausal women with over 25 years of follow-up. Participants will be drawn from two sub-cohorts embedded within the WHI using an incidence density sampling approach. Cancer survivors will be drawn from an existing NCI-funded survivorship cohort, the Life and Longevity After Cancer (LILAC) cohort, and cancer-free controls will be drawn from the WHI Long Life Study 2. The overall objective of this application is to examine the antecedents and consequences of low muscle mass in cancer survivors, using innovative methods to overcome major sources o