Cheng Chak Kwong, Gao Jun, Kang Lijing, Huang Yu
Department of Biomedical Sciences, City University of Hong Kong, Tat Chee Avenue, Hong Kong SAR, China.
Affiliated Qingyuan Hospital, The Sixth Clinical Medical School, Guangzhou Medical University, Qingyuan People's Hospital, Guangdong, China.
Aging Dis. 2024 Jun 10;16(3):1576-1585. doi: 10.14336/AD.2024.0384.
As a major risk factor for cardiometabolic diseases, aging refers to a gradual decline in physiological function, characterized with 12 conspicuous hallmarks, like telomere attrition, chronic inflammation, and dysbiosis. Common vascular aging hallmarks include endothelial dysfunction, telomere dysfunction, and vascular inflammation. In this study, we sought to test the hypothesis that young-derived gut microbiota retards vascular aging hallmarks and metabolic impairments in aged hosts. We also aimed to study the therapeutic efficacy of young microbiota in hosts of different ages. Fecal microbiota transplantation (FMT) from young to aged or middle-aged C57BL/6 mice was conducted for 6 consecutive weeks after antibiotic pretreatment. Endothelium-dependent relaxations (EDRs) in mouse arteries were determined by wire myography. Inflammation and AMPK/SIRT1 signaling in mouse aortas and intestines were studied by biochemical assays. The telomere function of aortas and intestines, in terms of telomerase reverse transcriptase expression, telomerase activity, and relative telomere length, were also studied. FMT significantly reverted vascular dysfunction and metabolic impairments in middle-aged mice than in aged mice. Besides, FMT significantly reverted inflammation and telomere dysfunction in aortas and intestines of middle-aged mice. Improved intestinal barrier function and activated AMPK/SIRT1 signaling potentially underlie benefits of FMT. The findings imply gut-vascular connection as potential target against age-associated cardiometabolic disorders, highlight crosstalk among aging hallmarks, and suggest a critical timepoint for efficacy of anti-aging interventions.
作为心脏代谢疾病的主要风险因素，衰老指的是生理功能逐渐衰退，其特征为12个明显的标志，如端粒磨损、慢性炎症和微生物群落失调。常见的血管衰老标志包括内皮功能障碍、端粒功能障碍和血管炎症。在本研究中，我们试图验证这样一个假设：源自年轻个体的肠道微生物群可延缓老年宿主的血管衰老标志和代谢损伤。我们还旨在研究年轻微生物群在不同年龄宿主中的治疗效果。在抗生素预处理后，对年轻C57BL/6小鼠向老年或中年C57BL/6小鼠进行连续6周的粪便微生物群移植（FMT）。通过线肌描记法测定小鼠动脉中的内皮依赖性舒张（EDR）。通过生化分析研究小鼠主动脉和肠道中的炎症以及AMPK/SIRT1信号通路。还研究了主动脉和肠道在端粒酶逆转录酶表达、端粒酶活性和相对端粒长度方面的端粒功能。与老年小鼠相比，FMT能更显著地逆转中年小鼠的血管功能障碍和代谢损伤。此外，FMT能显著逆转中年小鼠主动脉和肠道中的炎症和端粒功能障碍。肠道屏障功能的改善和AMPK/SIRT1信号通路的激活可能是FMT产生益处的潜在原因。这些发现表明肠道与血管的联系是对抗与年龄相关的心脏代谢疾病的潜在靶点，突出了衰老标志之间的相互作用，并提示了抗衰老干预措施起效的关键时间点。
