The Danish Twin Registry and The Danish Aging Research Center, Department of Public Health, University of Southern Denmark, Odense C, Denmark; Department of Clinical Genetics, Odense University Hospital, Odense C, Denmark.
Department of Clinical Genetics, Odense University Hospital, Odense C, Denmark; Department of Clinical Research, Human Genetics, University of Southern Denmark, Odense C, Denmark.
Neurobiol Aging. 2019 Dec;84:141-147. doi: 10.1016/j.neurobiolaging.2019.08.019. Epub 2019 Aug 26.
Only few studies have investigated the genomewide transcriptome of normative cognitive aging. We therefore aimed at investigating blood gene expression patterns associated with cognitive aging using a population-based sample of 235 middle-aged monozygotic twin pairs with longitudinal data on cognitive function. This unique setup enabled examination of gene expression differences associated with individual and intrapair differences in cognitive level and change while controlling for underlying genetic variation and shared early environment. Overall, increased expression of several gene sets was found to strongly correlate with a lower cognitive level and cognitive decline. The most significantly correlated gene sets were related to protein metabolism, translation, RNA metabolism, infectious disease, and the immune system, which are all processes previously linked to transcription signatures of pathological and normal brain aging, and aging in blood. The results of our study thus suggest that gene expression patterns of cognitive level and decline in our sample mirror those seen in cognitively impaired individuals, which could point toward a more generic response to cognitive aging and aging in general.
仅有少数研究调查了正常认知衰老的全基因组转录组。因此，我们旨在使用基于人群的 235 对中年同卵双胞胎的纵向认知功能数据，研究与认知衰老相关的血液基因表达模式。这种独特的设置使我们能够检查与个体和个体内认知水平和变化相关的基因表达差异，同时控制潜在的遗传变异和共同的早期环境。总的来说，一些基因集的表达增加与认知水平较低和认知能力下降强烈相关。相关性最强的基因集与蛋白质代谢、翻译、RNA 代谢、传染病和免疫系统有关，这些过程都与病理性和正常大脑衰老以及血液衰老的转录特征有关。因此，我们的研究结果表明，我们样本中认知水平和下降的基因表达模式反映了认知障碍个体的情况，这可能表明对认知衰老和一般衰老的反应更为普遍。
