Instituto de Investigación Sanitaria del Hospital Universitario de Getafe, Getafe, Spain.
Servicio de Histología-Investigación, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Hospital Ramón y Cajal, Madrid, Spain.
J Am Med Dir Assoc. 2017 Aug 1;18(8):734.e1-734.e7. doi: 10.1016/j.jamda.2017.04.019. Epub 2017 Jun 21.
Specific mechanisms underlying frailty syndrome are not well known. Frailty can be viewed as a loss of functional reserve resulting in increased vulnerability to stressors. We hypothesize that pathways regulating cellular response to stress are potential players in the development of frailty. The aim of this study was to evaluate the association of the expression of certain genes related to cellular response to stress with the presence of frailty in older patients.
A sample of 350 individuals aged 65 years or older (22% frail) was selected from the Toledo Study of Healthy Aging. RNA was extracted from blood and retro-transcribed into complementary DNA. TaqMan Low density Arrays were used for the measurement of expression of genes implicated in cellular response to oxidative stress, genes implicated in inflammation, genes implicated in vascular physiology, and genes related to hypoxia. For data analysis, a logistic regression model was used to assess the relationship of gene expression and frailty.
Among the analyzed genes, lower expression of genes related to cellular response to hypoxia (hypoxia inducible factor-1α) or to cellular response to oxidative stress (nuclear factor erythroid 2-related factor 2 and its target genes heme oxygenase-2, thioredoxin reductase-1, and superoxide dismutase-2), but not to those related to inflammation or vascular physiology, were significantly associated with the presence of frailty after adjustment for age and sex. These associations remained significant after adjustment by type 2 diabetes and Charlson index of comorbidities. Lower expressions of genes involved in cellular response to stress were also associated with increased risk of functional impairment.
Reduced expression of several genes implicated in cellular response to oxidative stress or hypoxia is significantly associated with the presence of frailty. These results help to fill the gap of knowledge of this evolving field and provide targets for intervention to promote health and independence in the elderly.
衰弱综合征的具体机制尚不清楚。衰弱可以被视为功能储备的丧失，导致对压力源的易感性增加。我们假设，调节细胞对应激反应的途径可能是导致衰弱的潜在因素。本研究旨在评估与细胞对应激反应相关的某些基因的表达与老年患者衰弱的发生之间的关系。
从托莱多健康老龄化研究中选择了 350 名年龄在 65 岁或以上的个体（22%衰弱）作为样本（22%衰弱）。从血液中提取 RNA，并逆转录为互补 DNA。TaqMan 低密度阵列用于测量参与细胞对应激反应的基因、参与炎症的基因、参与血管生理学的基因以及与缺氧相关的基因的表达。为了数据分析，使用逻辑回归模型来评估基因表达与衰弱之间的关系。
在所分析的基因中，与细胞缺氧反应（缺氧诱导因子-1α）或细胞对应激反应（核因子红细胞 2 相关因子 2 及其靶基因血红素加氧酶-2、硫氧还蛋白还原酶-1 和超氧化物歧化酶-2）相关的基因表达降低与衰弱的发生显著相关，调整年龄和性别后。在调整 2 型糖尿病和合并症的 Charlson 指数后，这些关联仍然显著。参与细胞应激反应的基因表达降低也与功能障碍风险增加相关。
参与细胞对应激反应的几个基因的表达降低与衰弱的发生显著相关。这些结果有助于填补这一不断发展领域的知识空白，并为促进老年人健康和独立的干预提供了目标。
