CCAAT-enhancer-binding protein-beta expression in vivo is associated with muscle strength.
CCAAT-enhancer-binding protein-beta expression in vivo is associated with muscle strength.
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DOI：
10.1111/j.1474-9726.2011.00782.x
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发表时间：
2012-04
期刊：
影响因子：
7.8
通讯作者：
Melzer D
中科院分区：
文献类型：
--
作者：
Harries LW;Pilling LC;Hernandez LD;Bradley-Smith R;Henley W;Singleton AB;Guralnik JM;Bandinelli S;Ferrucci L;Melzer D
肌肉力量下降是衰老的核心特征。已经假设了几种机制，包括 CCAAT/增强子结合蛋白-β (C/EBP-β) 在微损伤后触发巨噬细胞介导的肌纤维再生，这在小鼠模型中得到了证实。我们的目的是确定与成年人群肌肉力量相关的体内循环白细胞基因表达变化。我们使用 InCHIANTI 研究参与者（30-104 岁）的外周血 RNA 样本进行了全基因组表达微阵列筛查。使用针对多个混杂因素调整的模型，记录的表达强度随肌肉力量回归。主要结果通过实时 PCR 进行验证。短期身体表现电池评分 (SPPB) 测试步行速度、椅子站立和平衡。 CEBPB表达水平与肌肉力量相关（β系数= 0.20560，p=1.03*10−6，错误发现率q=0.014）。 CEBPB 表达最低三分位的 70 岁男性的估计握力为 35.2 公斤，而最高三分位的握力为 41.2 公斤。 CEBPB 表达还与髋部、膝部、踝部和肩部力量以及 SPPB 表现评分相关（p=0.018）。还注意到 TGFB3 (p=3.4*10−5, q=0.12) 和 CEBPD 表达 (p=9.67E−5, q=0.18) 之间存在接近研究范围的关联，但 CEBPA 表达则不然。我们在此报告了一项新发现，即体内循环白细胞来源的 RNA 样本中 CEBPB 表达升高与人类更大的肌肉力量和更好的身体表现相关。这种关联可能与 CEBPB 触发肌肉修复的小鼠模型证据一致：如果这种机制得到证实，它可能为保护和增强老化肌肉的干预提供目标。
Declining muscle strength is a core feature of aging. Several mechanisms have been postulated, including CCAAT/enhancer-binding protein-beta (C/EBP-β) triggered macrophage-mediated muscle fibre regeneration after micro-injury, evidenced in a mouse model. We aimed to identify in-vivo circulating leukocyte gene expression changes associated with muscle strength in the human adult population. We undertook a genome wide expression microarray screen, using peripheral blood RNA samples from InCHIANTI study participants (ages 30–104 yrs). Logged expression intensities were regressed with muscle strength using models adjusted for multiple confounders. Key results were validated by real-time PCR. The Short Physical Performance Battery score (SPPB) tested walk speed, chair stand and balance. CEBPB expression levels were associated with muscle strength (beta coefficient = 0.20560, p=1.03*10−6, false discovery rate q=0.014). The estimated handgrip strength in 70 year old men in the lowest CEBPB expression tertile was 35.2 kg compared to 41.2 kg in the top tertile. CEBPB expression was also associated with hip, knee, ankle and shoulder strength and the SPPB performance score (p=0.018). Near study-wide associations were also noted for TGFB3 (p=3.4*10−5, q=0.12) and CEBPD expression (p=9.67E−5, q=0.18) but not for CEBPA expression. We report here a novel finding that raised CEBPB expression in circulating leukocyte derived RNA samples in-vivo is associated with greater muscle strength and better physical performance in humans. This association may be consistent with mouse model evidence of CEBPB triggered muscle repair: if this mechanism is confirmed it may provide a target for intervention to protect and enhance aging muscle.
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