Veterans with cancer are susceptible to muscle wasting disorders including both cachexia (chronic disease related) and sarcopenia (age related). The cumulative effect of this muscle wasting is both poor response to cancer treatments and high risk of physical disability. Unfortunately, clinical trials for cancer related cachexia have encountered several barriers, including lack of precise diagnosis and classification of true muscle wasting in cancer patients. Current approaches to cachexia diagnosis include body weight and indirect body composition measures via imaging modalities. However, these approaches are flawed, lack specificity to muscle, and do not correlate well with physical functional outcomes. D3-creatine (D3-Cr) has recently emerged as novel biomarker of functional skeletal muscle mass and correlates well with muscle and functional outcomes in patients with age-related sarcopenia. Thus, D3-creatine has been suggested as a power tool for estimating muscle mass for future clinical trials, including in cancer patients. However, D3-creatine has not been specifically tested in the context of cancer muscle wasting, and others have postulated that the relationship between D3-creatine and total muscle mass is confounded by muscle wasting pathology, including cachexia and sarcopenia. Further study of D3-creatine is needed at the pre-clinical level before it can be applied broadly in the cancer population. The major scientific goal in this study is to determine the specific utility of D3-Cr in predicting muscle wasting and function in the context of cachexia, sarcopenia, and both during cancer. Using our novel longitudinal pre-clinical mouse model of cancer-associated cachexia, in Aim 1, we will compare D3-Cr levels in mature animals (20 weeks old) with and without cancer cachexia. We will then correlate D3-Cr levels with physiologic cross-sectional area (PCSA) of an array of lower extremity muscles as well as physical function. Function will be assessed using grip strength, treadmill time to fatigue, and maze-based assays for assessing gait speed and cognitive function. We hypothesize that D3-Cr levels will strongly correlate with PCSA and physical function measures in cancer animals. In Aim 2, we will assess D3-Cr levels, PCSA, and physical function in aged animals (90 weeks old) with and without cancer cachexia. We again hypothesize that D3-Cr levels will strongly correlate with PCSA and physical function measures in aged cancer animals. However, we also hypothesize that in a two-way ANOVA of cancer and age, that there will be a significant association between D3-CR and the interaction of these two variables. By completing this pre-clinical work, we will establish the specific pathologic conditions related to cancer in which D3-Cr may be used to predict muscle wasting. More directed future clinical studies can then be designed for the application of D3-Cr as a biomarker of cancer related muscle wasting.