Tello-Palencia Marco A, Yang Tony, Sularz Olga, Demers Louis Erik, Ma Yuexi, Boycott Cayla, Zhang Huiying Amelie, Lubecka-Gajewska Katarzyna, Kumar Sadhri, Ramsey Benjamin S, Torregrosa-Allen Sandra, Elzey Bennett D, Lanman Nadia Atallah, Korthauer Keegan, Stefanska Barbara
Department of Statistics, Faculty of Science, the University of British Columbia, Vancouver, BC, V6T 1Z4, Canada.
Food, Nutrition and Health Program, Faculty of Land and Food Systems, the University of British Columbia, Vancouver, BC, V6T 1Z4, Canada.
Mol Nutr Food Res. 2024 Dec;68(24):e2400662. doi: 10.1002/mnfr.202400662. Epub 2024 Nov 19.
Polyphenols 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.
In 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.
The 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.
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促长寿作用仍然未知。由于长寿研究表明人类血液中存在与年龄相关的转录组特征，当前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，最终带来促长寿益处。
在本研究中，进行了RNA测序以确定食用补充植物雌激素饮食的健康大鼠全血中基因表达的全转录组变化。应用直系同源细胞反卷积来分析组学数据。研究发现，PTS导致基因表达格局的变化，且PTS靶基因与对抗衰老特征的功能相关，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稳态丧失。这些功能通过多种途径在抗炎作用下共同作用，包括免疫代谢，其中细胞代谢的变化（如核糖体生物发生）会影响免疫系统。
这些发现为临床前和临床长寿研究提供了理论依据，并鼓励对PTS在维持细胞稳态、延缓衰老过程和改善慢性炎症状况方面进行研究。
