Open AccessTrimethylamine‐ N ‐oxide promotes brain aging and cognitive impairment in mice
Author(s) -
Li Dang,
Ke Yilang,
Zhan Rui,
Liu Changjie,
Zhao Mingming,
Zeng Aiping,
Shi Xiaoyun,
Ji Liang,
Cheng Si,
Pan Bing,
Zheng Lemin,
Hong Huashan
Publication year - 2018
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12768
Subject(s) - trimethylamine n oxide , senescence , hippocampal formation , hippocampus , brain aging , biology , aging brain , cognitive decline , endocrinology , medicine , neuroscience , cognition , dementia , disease , microbiology and biotechnology , biochemistry , trimethylamine
Summary 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 ( SAMP 8) and age‐matched senescence‐accelerated mouse resistant 1 ( SAMR 1) mice for 16 weeks. We found that the plasma levels of TMAO increased in both the elderly and the aged mice. Compared with SAMR 1‐control mice, SAMP 8‐control mice exhibited a brain aging phenotype characterized by more senescent cells in the hippocampal CA 3 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 SAMR 1 and SAMP 8 mice, respectively. Our findings suggested that TMAO could induce brain aging and age‐related cognitive dysfunction in SAMR 1 mice and aggravate the cerebral aging process of SAMP 8 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.