Aged Gut Microbiome Induces Metabolic Impairment and Hallmarks of Vascular and Intestinal Aging in Young Mice.

IF 6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Antioxidants Pub Date : 2024-10-17 DOI:10.3390/antiox13101250
Chak-Kwong Cheng, Lianwei Ye, Yuanyuan Zuo, Yaling Wang, Li Wang, Fuyong Li, Sheng Chen, Yu Huang
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Abstract

Aging, an independent risk factor for cardiometabolic diseases, refers to a progressive deterioration in physiological function, characterized by 12 established hallmarks. Vascular aging is driven by endothelial dysfunction, telomere dysfunction, oxidative stress, and vascular inflammation. This study investigated whether aged gut microbiome promotes vascular aging and metabolic impairment. Fecal microbiome transfer (FMT) was conducted from aged (>75 weeks old) to young C57BL/6 mice (8 weeks old) for 6 weeks. Wire myography was used to evaluate endothelial function in aortas and mesenteric arteries. ROS levels were measured by dihydroethidium (DHE) staining and lucigenin-enhanced chemiluminescence. Vascular and intestinal telomere function, in terms of relative telomere length, telomerase reverse transcriptase expression and telomerase activity, were measured. Systemic inflammation, endotoxemia and intestinal integrity of mice were assessed. Gut microbiome profiles were studied by 16S rRNA sequencing. Some middle-aged mice (40-42 weeks old) were subjected to chronic metformin treatment and exercise training for 4 weeks to evaluate their anti-aging benefits. Six-week FMT impaired glucose homeostasis and caused vascular dysfunction in aortas and mesenteric arteries in young mice. FMT triggered vascular inflammation and oxidative stress, along with declined telomerase activity and shorter telomere length in aortas. Additionally, FMT impaired intestinal integrity, and triggered AMPK inactivation and telomere dysfunction in intestines, potentially attributed to the altered gut microbial profiles. Metformin treatment and moderate exercise improved integrity, AMPK activation and telomere function in mouse intestines. Our data highlight aged microbiome as a mechanism that accelerates intestinal and vascular aging, suggesting the gut-vascular connection as a potential intervention target against cardiovascular aging and complications.

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衰老的肠道微生物组诱发年轻小鼠的代谢损伤以及血管和肠道衰老的特征
衰老是心血管代谢疾病的一个独立风险因素,是指生理功能的逐渐退化,有 12 个既定的特征。血管老化是由内皮功能障碍、端粒功能障碍、氧化应激和血管炎症驱动的。本研究调查了老年肠道微生物组是否会促进血管老化和代谢损伤。研究人员将老龄小鼠(>75 周龄)的粪便微生物组转移到年轻的 C57BL/6 小鼠(8 周龄)体内,为期 6 周。用线肌电图评估主动脉和肠系膜动脉的内皮功能。ROS水平通过二氢乙锭(DHE)染色和荧光素增强化学发光进行测量。通过端粒相对长度、端粒酶逆转录酶表达和端粒酶活性测量了血管和肠道端粒功能。对小鼠的全身炎症、内毒素血症和肠道完整性进行了评估。通过 16S rRNA 测序研究了肠道微生物组概况。对一些中年小鼠(40-42 周大)进行了为期 4 周的慢性二甲双胍治疗和运动训练,以评估它们的抗衰老功效。为期六周的FMT损害了葡萄糖稳态,并导致年轻小鼠主动脉和肠系膜动脉血管功能障碍。FMT引发血管炎症和氧化应激,同时导致端粒酶活性下降和主动脉端粒长度缩短。此外,FMT还会损害肠道完整性,引发肠道中AMPK失活和端粒功能障碍,这可能是由于肠道微生物谱发生了改变。二甲双胍治疗和适度运动改善了小鼠肠道的完整性、AMPK活化和端粒功能。我们的数据强调了老化的微生物组是加速肠道和血管老化的机制,这表明肠道与血管的联系是防止心血管老化和并发症的潜在干预目标。
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来源期刊
Antioxidants
Antioxidants Biochemistry, Genetics and Molecular Biology-Physiology
CiteScore
10.60
自引率
11.40%
发文量
2123
审稿时长
16.3 days
期刊介绍: Antioxidants (ISSN 2076-3921), provides an advanced forum for studies related to the science and technology of antioxidants. It publishes research papers, reviews and communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. Electronic files and software regarding the full details of the calculation or experimental procedure, if unable to be published in a normal way, can be deposited as supplementary electronic material.
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