Faculty of Medical Sciences, Goce Delcev University, 2000 Stip, North Macedonia.
Institute for Adriatic Crops and Karst Reclamation, 21000 Split, Croatia.
Ageing Res Rev. 2022 Aug;79:101649. doi: 10.1016/j.arr.2022.101649. Epub 2022 May 18.
Cardiovascular and metabolic disorders present major causes of mortality in the ageing population. Polyphenols present in human diets possess cardiometabolic protective properties, however their underlying molecular mechanisms in humans are still not well identified. Even though preclinical and in vitro studies advocate that these bioactives can modulate gene expression, most studies were performed using targeted approaches. With the objective to decipher the molecular mechanisms underlying polyphenols cardiometabolic preventive properties in humans, we performed integrative multi-omic bioinformatic analyses of published studies which reported improvements of cardiometabolic risk factors following polyphenol intake, together with genomic analyses performed using untargeted approach. We identified 5 studies within our criteria and nearly 5000 differentially expressed genes, both mRNAs and miRNAs, in peripheral blood cells. Integrative bioinformatic analyses (e.g. pathway and gene network analyses, identification of transcription factors, correlation of gene expression profiles with those associated with diseases and drug intake) revealed that these genes are involved in the processes such as cell adhesion and mobility, immune system, metabolism, or cell signaling. We also identified 27 miRNAs known to regulate processes such as cell cytoskeleton, chemotaxis, cell signaling, or cell metabolism. Gene expression profiles negatively correlated with expression profiles of cardiovascular disease patients, while a positive correlation was observed with gene expression profiles following intake of drugs against cardiometabolic disorders. These analyses further advocate for health protective effects of these bioactives against age-associated diseases. In conclusion, polyphenols can exert multi-genomic modifications in humans and use of untargeted methods coupled with bioinformatic analyses represent the best approach to decipher molecular mechanisms underlying healthy-ageing effects of these bioactives.
心血管和代谢紊乱是老龄化人口死亡的主要原因。人类饮食中的多酚具有心脏代谢保护特性，但它们在人体中的潜在分子机制仍未得到很好的阐明。尽管临床前和体外研究表明这些生物活性物质可以调节基因表达，但大多数研究都是使用靶向方法进行的。为了解决多酚对人类心脏代谢的预防作用的分子机制，我们对报道多酚摄入可改善心脏代谢危险因素的已发表研究进行了综合多组学生物信息学分析，并结合使用非靶向方法进行了基因组分析。我们根据标准确定了 5 项研究，涉及近 5000 个差异表达基因，包括外周血细胞中的 mRNA 和 miRNA。综合生物信息学分析（例如途径和基因网络分析、转录因子鉴定、基因表达谱与与疾病和药物摄入相关的基因表达谱的相关性）表明，这些基因参与细胞黏附与迁移、免疫系统、代谢或细胞信号转导等过程。我们还鉴定了 27 个已知调节细胞骨架、趋化作用、细胞信号转导或细胞代谢等过程的 miRNA。基因表达谱与心血管疾病患者的表达谱呈负相关，而与心脏代谢紊乱药物摄入后的基因表达谱呈正相关。这些分析进一步证明了这些生物活性物质对年龄相关疾病的健康保护作用。总之，多酚可以在人类中发挥多基因组修饰作用，使用非靶向方法结合生物信息学分析是揭示这些生物活性物质对健康衰老影响的分子机制的最佳方法。
