The D3-creatine dilution method non-invasively measures muscle mass in mice |
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Authors: | Lauren Wimer Elena Goncharova Sofiya Galkina Edna Nyangau Mahalakshmi Shankaran Asia Davis Leandro Prado Maria Castro Munoz Sharon Epstein Cavan Patterson Nicholas Shaum Mark Hellerstein William Evans Simon Melov |
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Institution: | 1. Buck Institute for Research on Aging, Novato, California, USA;2. Department of Nutritional Sciences and Toxicology, University of California, Berkeley, California, USA;3. Astera Institute, Berkeley, California, USA |
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Abstract: | Developing accurate methods to quantify age-related muscle loss (sarcopenia) could greatly accelerate development of therapies to treat muscle loss in the elderly, as current methods are inaccurate or expensive. The current gold standard method for quantifying sarcopenia is dual-energy X-ray absorptiometry (DXA) but does not measure muscle directly—it is a composite measure quantifying “lean mass” (muscle) excluding fat and bone. In humans, DXA overestimates muscle mass, which has led to erroneous conclusions about the importance of skeletal muscle in human health and disease. In animal models, DXA is a popular method for measuring lean mass. However, instrumentation is expensive and is potentially limited by anesthesia concerns. Recently, the D3-creatine (D3Cr) dilution method for quantifying muscle mass was developed in humans and rats. This method is faster, cheaper, and more accurate than DXA. Here, we demonstrate that the D3Cr method is a specific assay for muscle mass in mice, and we test associations with DXA and body weight. We evaluated the D3Cr method compared to DXA-determined lean body mass (LBM) in aged mice and reported that DXA consistently overestimates muscle mass with age. Overall, we provide evidence that the D3Cr dilution method directly measures muscle mass in mice. Combined with its ease of use, accessibility, and non-invasive nature, the method may prove to more quickly advance development of preclinical therapies targeting sarcopenia. |
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Keywords: | aging mice sarcopenia skeletal muscle |
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