Bigossi Giorgia, Marcozzi Serena, Giuliani Maria Elisa, Lai Giovanni, Bartozzi Beatrice, Orlando Fiorenza, Gerosa Laura, Malvandi Amir Mohammad, Putavet Diana, Bouma Esmée, de Keizer Peter L J, Lombardi Giovanni, Malavolta Marco
Advanced Technology Center for Aging Research and Geriatric Mouse Clinic, IRCCS INRCA, Ancona, Italy.
Advanced Technology Center for Aging Research, IRCCS INRCA, Ancona, Italy.
J Cachexia Sarcopenia Muscle. 2025 Oct;16(5):e70050. doi: 10.1002/jcsm.70050.
Grip strength is a key functional marker of musculoskeletal aging, widely used to assess sarcopenia. In preclinical research, multiple measurement methods are often combined to enhance reliability, but standardization remains challenging. To improve measurement robustness, we previously developed a composite strength score (SS5) that integrates five different grip strength tests into a single variable. While SS5 provides a comprehensive evaluation, its implementation is time-consuming, limiting feasibility in large-scale studies. In this study, we also examine two simplified composite scores, SS2 and SS3, as potential streamlined alternatives. Additionally, although normalizing grip strength to body weight is widely used, its appropriateness in geriatric mouse models has never been formally validated.
Forelimb grip strength was assessed in a cohort of 160-aged C57BL/6J mice using five methods: Weight Lift Tests (Deacon protocol with sponge weights and a modified version with metal wire weights), the Cage Lift Test and the Grip Strength Meter (trapeze bar and grid). Additionally, a cross-sectional group of 173 mice was analysed to assess the correlation between grip strength and muscle size. Each method was evaluated for its correlation with age, ability to detect sex differences, variability and association with muscle size.
All methods strongly correlated with age (-0.518 ≤ r ≤ -0.306). The Grip Strength Meter (trapeze bar) and modified Deacon method were the most effective in detecting sex differences (p < 0.001). While all methods correlated with muscle size (0.153 ≤ r ≤ 0.332), the modified Deacon method and Grip Strength Meter showed the strongest associations. The mean coefficient of variation (CV%) ranged from 7% to 17%, demonstrating good repeatability. Notably, despite being widely used, normalization of grip strength to body weight was found to introduce bias in geriatric mice, as age-related weight loss distorts strength assessments. Absolute values proved to be a more reliable measure. To improve efficiency while maintaining reliability, we developed two new composite scores (SS2 and SS3) by integrating a subset of methods from SS5. These scores preserved the strong correlation with age observed in SS5 while reducing the number of required tests, enhancing feasibility.
Combining multiple grip strength assessments improves measurement reliability in aging studies. The newly proposed SS2 and SS3 scores provide a streamlined yet robust alternative to SS5, improving standardization and facilitating future comparisons in preclinical sarcopenia research. Our findings also challenge the routine normalization of grip strength to body weight in geriatric mice, emphasizing the importance of using absolute values to avoid bias.
握力是肌肉骨骼衰老的关键功能指标,广泛用于评估肌肉减少症。在临床前研究中,常结合多种测量方法以提高可靠性,但标准化仍具有挑战性。为提高测量的稳健性,我们先前开发了一种综合强度评分(SS5),它将五种不同的握力测试整合为一个单一变量。虽然SS5提供了全面评估,但其实施耗时,限制了大规模研究的可行性。在本研究中,我们还考察了两种简化的综合评分SS2和SS3,作为潜在的简化替代方案。此外,尽管将握力除以体重进行标准化的方法被广泛使用,但其在老年小鼠模型中的适用性从未得到正式验证。
使用五种方法评估了160只老年C57BL/6J小鼠队列的前肢握力:举重测试(使用海绵重量的迪肯协议和使用金属丝重量的改良版本)、笼式举升测试和握力计(吊环和网格)。此外,分析了一个包含173只小鼠的横断面组,以评估握力与肌肉大小之间的相关性。评估了每种方法与年龄的相关性、检测性别差异的能力、变异性以及与肌肉大小的关联。
所有方法与年龄均呈强相关(-0.518≤r≤-0.306)。握力计(吊环)和改良迪肯方法在检测性别差异方面最有效(p<0.001)。虽然所有方法都与肌肉大小相关(0.153≤r≤0.332),但改良迪肯方法和握力计显示出最强的关联。平均变异系数(CV%)在7%至17%之间,表明重复性良好。值得注意的是,尽管广泛使用,但发现将握力除以体重进行标准化会在老年小鼠中引入偏差,因为与年龄相关的体重减轻会扭曲力量评估。绝对值被证明是更可靠的测量方法。为了在保持可靠性的同时提高效率,我们通过整合SS5中的一部分方法开发了两个新的综合评分(SS2和SS3)。这些评分保留了与SS5中观察到的与年龄的强相关性,同时减少了所需测试的数量,提高了可行性。
结合多种握力评估可提高衰老研究中的测量可靠性。新提出的SS2和SS3评分提供了一种比SS5更简化但稳健的替代方案,提高了标准化程度,并便于临床前肌肉减少症研究中的未来比较。我们的研究结果还对老年小鼠中常规将握力除以体重进行标准化提出了挑战,强调了使用绝对值以避免偏差的重要性。