National Institute on Aging, Clinical Research Branch, Longitudinal Studies Section, Baltimore, Maryland 21225, USA.
Rejuvenation Res. 2010 Feb;13(1):3-11. doi: 10.1089/rej.2009.0891.
Poor muscle strength is a major public health concern in older persons, predisposing to functional limitations, increased fall risk, and higher mortality. Understanding risk factors for muscle strength decline may offer opportunities for prevention and treatment. One of the possible causes of muscle strength decline is imbalance between catabolic and anabolic signaling. This study aims to examine whether high levels of multiple catabolic and low levels of multiple anabolic biomarkers predict accelerated decline of muscle strength.
In a representative sample of 716 men and women aged >or=65 years in the InCHIANTI study we measured C-reactive protein, interleukin-6 (IL-6), IL-1 receptor antagonist (IL-1RA), tumor necrosis factor-alpha receptor 1 as well as dehydroepiandrosterone sulfate (DHEA-S), insulin-like growth factor-1, and bioavailable testosterone. Biomarker values were divided into tertiles and the numbers of catabolic/anabolic biomarkers in the highest/lowest tertile were calculated. Hand-grip strength was measured at baseline and 3- and 6-year follow up.
In adjusted linear mixed models, higher concentration of IL-6 (p = 0.02) and IL-1RA (p = 0.04) as well as lower levels of DHEA-S (p = 0.01) predicted muscle strength decline. After combining all inflammatory markers, the rate of decline in grip strength was progressively greater with the increasing number of dysregulated catabolic biomarkers (p = 0.01). No effect on accelerated muscle strength decline was seen according to number of dysregulated anabolic hormones.
Having multiple elevated catabolic biomarkers is a better predictor of muscle strength decline than a single biomarker alone, suggesting that a catabolic dysregulation is at the core of the mechanism leading to muscle strength decline with aging.
肌肉力量弱是老年人的主要公共健康关注点,容易导致功能受限、跌倒风险增加和死亡率上升。了解肌肉力量下降的风险因素可能为预防和治疗提供机会。肌肉力量下降的一个可能原因是分解代谢和合成代谢信号之间的失衡。本研究旨在检验多种分解代谢标志物水平高和多种合成代谢标志物水平低是否预示着肌肉力量加速下降。
我们在 InCHIANTI 研究中,对 716 名年龄≥65 岁的男性和女性的代表性样本进行了研究,测量了 C 反应蛋白、白细胞介素-6(IL-6)、IL-1 受体拮抗剂(IL-1RA)、肿瘤坏死因子-α受体 1 以及硫酸脱氢表雄酮(DHEA-S)、胰岛素样生长因子-1 和生物可利用性睾酮。将生物标志物值分为三分位,并计算最高/最低三分位的分解代谢/合成代谢标志物数量。在基线和 3 年及 6 年随访时测量握力。
在调整后的线性混合模型中,IL-6(p = 0.02)和 IL-1RA(p = 0.04)浓度较高以及 DHEA-S(p = 0.01)水平较低预测肌肉力量下降。在结合所有炎症标志物后,随着调节不良的分解代谢标志物数量的增加,握力下降的速度逐渐加快(p = 0.01)。根据调节不良的合成代谢激素数量,对加速肌肉力量下降没有影响。
存在多种升高的分解代谢标志物是肌肉力量下降的更好预测指标,这表明分解代谢失调是导致衰老过程中肌肉力量下降的核心机制。