Frailty has been increasingly recognized as an important clinical syndrome in old age. The frailty syndrome is characterized by chronic inflammation, decreased functional and physiologic reserve, and increased vulnerability to stressors, leading to disability and mortality. However, molecular mechanisms that contribute to inflammation activation and regulation in frail older adults have not been investigated. To begin to address this, we conducted a pathway-specific gene array analysis of 367 inflammatory pathway genes by lipopolysaccharide (LPS)-challenged CD14(+) monocytes from 32 community-dwelling frail and age-, race-, and sex-paired nonfrail older adults (mean age 83 years, range 72-94). The results showed that ex vivo LPS-challenge induced average 2.0-fold or higher upregulated expression of 116 genes in frail participants and 85 genes in paired nonfrail controls. In addition, frail participants had 2-fold or higher upregulation in LPS-induced expression of 7 stress-responsive genes than nonfrail controls with validation by quantitative real time RT-PCR. These findings suggest upregulated expression of specific stress-responsive genes in monocyte-mediated inflammatory pathway in the syndrome of frailty with potential mechanistic and interventional implications.

中文翻译：

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LPS 攻击的 CD14(+) 单核细胞在体弱的老年人中上调应激反应性炎症通路基因的离体表达。

衰弱已越来越多地被认为是一种重要的老年临床综合征。虚弱综合征的特点是慢性炎症、功能和生理储备下降以及对压力源的脆弱性增加，导致残疾和死亡。然而，尚未研究导致体弱老年人炎症激活和调节的分子机制。为了开始解决这个问题，我们通过脂多糖 (LPS) 攻击的 CD14(+) 单核细胞对 367 个炎症通路基因进行了通路特异性基因阵列分析，这些单核细胞来自 32 个社区居住的体弱和年龄、种族和性别配对的非体弱老年人（平均年龄 83 岁，范围 72-94）。结果表明，离体 LPS 攻击诱导平均 2. 体弱参与者中 116 个基因和配对非体弱对照中 85 个基因的 0 倍或更高表达上调。此外，通过定量实时 RT-PCR 验证，体弱的参与者在 LPS 诱导的 7 个应激反应基因的表达上比非体弱的对照组高 2 倍或更高。这些发现表明，在虚弱综合征中，单核细胞介导的炎症通路中特定应激反应基因的表达上调，具有潜在的机械和干预意义。