Trimethylamine-N-oxide promotes brain aging and cognitive impairment in mice.
Trimethylamine-N-oxide promotes brain aging and cognitive impairment in mice.
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三甲胺-N-氧化物促进小鼠大脑衰老和认知障碍
DOI：
10.1111/acel.12768
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发表时间：
2018-08
期刊：
影响因子：
7.8
通讯作者：
Hong H
中科院分区：
文献类型：
--
作者：
Li D;Ke Y;Zhan R;Liu C;Zhao M;Zeng A;Shi X;Ji L;Cheng S;Pan B;Zheng L;Hong H
肠道微生物群可影响衰老进程，并可能调节与衰老相关的认知功能变化。三甲胺 - N - 氧化物（TMAO）作为肠道菌群的一种代谢产物，已被证明与心血管疾病及其他疾病密切相关。然而，TMAO与衰老，尤其是脑衰老之间的关系尚未完全阐明。为探究TMAO与脑衰老的关系，我们分析了人类和小鼠血浆中的TMAO水平，并对24周龄的快速老化小鼠品系8（SAMP8）和年龄匹配的抗快速老化小鼠1（SAMR1）连续16周给予外源性TMAO。我们发现，老年人和老龄小鼠血浆中的TMAO水平均有所升高。与SAMR1对照组小鼠相比，SAMP8对照组小鼠表现出脑老化表型，其特征为海马CA3区衰老细胞增多以及认知功能障碍。令人惊讶的是，TMAO处理增加了衰老细胞的数量，这些细胞主要是神经元，同时加剧了线粒体损伤和超氧化物的产生。此外，我们观察到TMAO处理通过抑制mTOR信号通路，增加了突触损伤并降低了突触可塑性相关蛋白的表达水平，分别诱导和加重了SAMR1和SAMP8小鼠与衰老相关的认知功能障碍。我们的研究结果表明，TMAO可诱导SAMR1小鼠脑衰老及与衰老相关的认知功能障碍，并加剧SAMP8小鼠的脑老化进程，这可能为肠道微生物群对脑老化进程的影响提供新的见解，并有助于通过调节肠道菌群代谢产物来延缓衰老。
Gut microbiota can influence the aging process and may modulate aging‐related changes in cognitive function. Trimethylamine‐N‐oxide (TMAO), a metabolite of intestinal flora, has been shown to be closely associated with cardiovascular disease and other diseases. However, the relationship between TMAO and aging, especially brain aging, has not been fully elucidated. To explore the relationship between TMAO and brain aging, we analysed the plasma levels of TMAO in both humans and mice and administered exogenous TMAO to 24‐week‐old senescence‐accelerated prone mouse strain 8 (SAMP8) and age‐matched senescence‐accelerated mouse resistant 1 (SAMR1) mice for 16 weeks. We found that the plasma levels of TMAO increased in both the elderly and the aged mice. Compared with SAMR1‐control mice, SAMP8‐control mice exhibited a brain aging phenotype characterized by more senescent cells in the hippocampal CA3 region and cognitive dysfunction. Surprisingly, TMAO treatment increased the number of senescent cells, which were primarily neurons, and enhanced the mitochondrial impairments and superoxide production. Moreover, we observed that TMAO treatment increased synaptic damage and reduced the expression levels of synaptic plasticity‐related proteins by inhibiting the mTOR signalling pathway, which induces and aggravates aging‐related cognitive dysfunction in SAMR1 and SAMP8 mice, respectively. Our findings suggested that TMAO could induce brain aging and age‐related cognitive dysfunction in SAMR1 mice and aggravate the cerebral aging process of SAMP8 mice, which might provide new insight into the effects of intestinal microbiota on the brain aging process and help to delay senescence by regulating intestinal flora metabolites.
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影响因子：
4
作者：
Li T;Chen Y;Gua C;Li X
通讯作者：
Li X
影响因子：
5.3
作者：
Candela, Marco;Biagi, Elena;De Vos, Willem M.
通讯作者：
De Vos, Willem M.
DOI：
10.1016/j.bbrc.2010.05.011
发表时间：
2010-06-11
影响因子：
3.1
作者：
Geng, Yi-Qun;Guan, Ji-Tian;Fu, Yu-Cai
通讯作者：
Fu, Yu-Cai
DOI：
10.1158/1055-9965.epi-16-0948
发表时间：
2017-06
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Guertin KA;Li XS;Graubard BI;Albanes D;Weinstein SJ;Goedert JJ;Wang Z;Hazen SL;Sinha R
通讯作者：
Sinha R
影响因子：
64.8
作者：
Claesson, Marcus J.;Jeffery, Ian B.;O'Toole, Paul W.
通讯作者：
O'Toole, Paul W.