Buck Institute for Research on Aging, Novato, California, USA.
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, California, USA.
Aging Cell. 2023 Aug;22(8):e13897. doi: 10.1111/acel.13897. Epub 2023 Jun 5.
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 D -creatine (D Cr) 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 D Cr method is a specific assay for muscle mass in mice, and we test associations with DXA and body weight. We evaluated the D Cr 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 D Cr 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.
开发准确的方法来量化与年龄相关的肌肉损失(肌肉减少症)可以极大地加速治疗老年人肌肉损失的疗法的发展,因为目前的方法不准确或昂贵。目前量化肌肉减少症的金标准方法是双能 X 射线吸收法(DXA),但它不能直接测量肌肉 - 它是一种衡量“瘦体重”(肌肉)的综合衡量标准,不包括脂肪和骨骼。在人类中,DXA 高估了肌肉量,这导致了对骨骼肌在人类健康和疾病中的重要性的错误结论。在动物模型中,DXA 是测量瘦肉量的常用方法。然而,仪器昂贵,并且可能受到麻醉问题的限制。最近,在人类和大鼠中开发了 D -肌酸(D Cr)稀释法来量化肌肉量。这种方法比 DXA 更快、更便宜、更准确。在这里,我们证明 D Cr 方法是小鼠肌肉量的特异性测定方法,并且我们测试了与 DXA 和体重的关联。我们评估了 D Cr 方法与 DXA 确定的瘦体重(LBM)在老年小鼠中的比较,并报告说 DXA 随着年龄的增长一致高估了肌肉量。总的来说,我们提供了证据表明 D Cr 稀释法直接测量了小鼠的肌肉量。结合其易用性、可及性和非侵入性,该方法可能会更快地推进针对肌肉减少症的临床前治疗的发展。