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Pterostilbene Targets Hallmarks of Aging in the Gene Expression Landscape in Blood of Healthy Rats
Molecular Nutrition & Food Research ( IF 4.5 ) Pub Date : 2024-11-20 , DOI: 10.1002/mnfr.202400662
Marco A. Tello‐Palencia, Tony Yang, Olga Sularz, Louis Erik Demers, Yuexi Ma, Cayla Boycott, Huiying Amelie Zhang, Katarzyna Lubecka‐Gajewska, Sadhri Kumar, Benjamin S. Ramsey, Sandra Torregrosa‐Allen, Bennett D. Elzey, Nadia Atallah Lanman, Keegan Korthauer, Barbara Stefanska

ScopePolyphenols from the phytoestrogen group, including pterostilbene (PTS), are known for their antioxidant, anti‐inflammatory, and anti‐cancer effects. In recent reports, phytoestrogens attenuate age‐related diseases; however, their pro‐longevity effects in healthy models in mammals remain unknown. As longevity research demonstrates age‐related transcriptomic signatures in human blood, the current study hypothesizes that phytoestrogen‐supplemented diet may induce changes in gene expression that ultimately confer pro‐longevity benefits.Methods and resultsIn the present study, RNA sequencing is conducted to determine transcriptome‐wide changes in gene expression in whole blood of healthy rats consuming diets supplemented with phytoestrogens. Ortholog cell deconvolution is applied to analyze the omics data. The study discovered that PTS leads to changes in the gene expression landscape and PTS‐target genes are associated with functions counteracting hallmarks of aging, including genomic instability, epigenetic alterations, compromised autophagy, mitochondrial dysfunction, deregulated nutrient sensing, altered intercellular interaction, and loss of proteostasis. These functions bridge together under anti‐inflammatory effects through multiple pathways, including immunometabolism, where changes in cellular metabolism (e.g., ribosome biogenesis) impact the immune system.ConclusionThe findings provide a rationale for pre‐clinical and clinical longevity studies and encourage investigations on PTS in maintaining cellular homeostasis, decelerating the process of aging, and improving conditions with chronic inflammation.

中文翻译:


紫檀芪靶向健康大鼠血液中基因表达景观中的衰老标志



Scope来自植物雌激素组的多酚,包括紫檀芪 (PTS),以其抗氧化、抗炎和抗癌作用而闻名。在最近的报道中,植物雌激素可以减轻与年龄相关的疾病;然而,它们在哺乳动物健康模型中的长寿效应仍然未知。随着长寿研究表明人类血液中存在与年龄相关的转录组特征,目前的研究假设补充植物雌激素的饮食可能会诱导基因表达的变化,最终带来长寿的好处。方法和结果在本研究中,进行 RNA 测序以确定食用补充植物雌激素的饮食的健康大鼠全血中基因表达的转录组范围变化。应用 Ortholog 细胞反卷积来分析组学数据。研究发现,PTS 导致基因表达景观发生变化,PTS 靶基因与抵消衰老标志的功能有关,包括基因组不稳定、表观遗传改变、自噬受损、线粒体功能障碍、营养感应失调、细胞间相互作用改变和蛋白质平衡丧失。在抗炎作用下,这些功能通过多种途径(包括免疫代谢)连接在一起,其中细胞代谢的变化(例如核糖体生物发生)会影响免疫系统。结论这些发现为临床前和临床寿命研究提供了基本原理,并鼓励研究 PTS 在维持细胞稳态、减缓衰老过程和改善慢性炎症状况方面的研究。
更新日期:2024-11-20
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