郑乐民+洪华山:菌群代谢物TMAO或促进脑衰老与认知损伤

Aging Cell

5/10/18Article

6.714

影响因子

原标题:氧化三甲胺促进小鼠的脑衰老与认知损伤

① 在衰老的人及小鼠的血浆中,氧化三甲胺的水平均上升;② 氧化三甲胺可增加小鼠体内衰老细胞的数量(主要是神经元),引起了小鼠海马CA3区域中的神经元衰老,并损伤海马CA1区域的超微结构;③ 氧化三甲胺可增加小鼠的线粒体损伤及超氧化物的产生;④ 另外,氧化三甲胺处理可增加突触损伤,并通过抑制mTOR信号通路,降低突触可塑性相关蛋白的表达水平,从而引起并加剧衰老相关的认知障碍。

衰老 氧化三甲胺

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Title:
Trimethylamine-N-oxide promotes brain aging and cognitive impairment in mice

DOI:
10.1111/acel.12768

Abstract & Authors展开

Abstract:
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.

All Authors:
Dang Li,Yilang Ke,Rui Zhan,Changjie Liu,Mingming Zhao,Aiping Zeng,Xiaoyun Shi,Liang Ji,Si Cheng,Bing Pan,Lemin Zheng,Huashan Hong

First Authors:
Dang Li,Yilang Ke

Correspondence:
Lemin Zheng,Huashan Hong

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