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Trimethylamine N-oxide: role in cell senescence and age-related diseases

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  • Published:
European Journal of Nutrition Aims and scope Submit manuscript

Abstract

Introduction

Hayflick and Moorhead first demonstrated cell senescence as the irreversible growth arrest of cells after prolonged cultivation. Telomere shortening and oxidative stress are the fundamental mechanisms that drive cell senescence. Increasing studies have shown that TMAO is closely associated with cellular aging and age-related diseases. An emerging body of evidence from animal models, especially mice, has identified that TMAO contributes to senescence from multiple pathways and appears to accelerate many neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease. However, the specific mechanism of how TMAO speeds aging is still not completely clear.

Material and methods

In this review, we summarize some key findings in TMAO, cell senescence, and age-related diseases. We focused particular attention on the potential mechanisms for clinical transformation to find ways to interfere with the aging process.

Conclusion

TMAO can accelerate cell senescence by causing mitochondrial damage, superoxide formation, and promoting the generation of pro-inflammatory factors.

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There are no original data in our manuscript.

Abbreviations

1H-NMR:

Proton nuclear magnetic resonance spectrometry

Aβ:

β-Amyloid peptide

AD:

Alzheimer’s disease

AS:

Atherosclerosis

βCTF:

β-Secretase C-terminal fragment

CHD:

Chow diet

CSF:

Cerebrospinal fluid

cntA/B:

Carnitine monooxygenase

cutC/D:

Choline-TMA lyase

DAMPs:

Damage-associated molecular patterns

DBM:

3,3-Dimethyl-1-butanol

DDR:

DNA damage response

DMB:

3,3-Dimethyl-1-butanol

DNA-SCARS:

DNA segments with chromatin alterations reinforcing senescence

EC:

Endothelial cell

ECM:

Extracellular matrix

ER:

Endoplasmic reticulum

FMO3:

Flavin-containing monooxygenase 3

GBB:

γ-Butyrobetaine

hCETP:

Human cholesterol ester transfer protein

HFD:

High-fat diet

HFHC:

High fat and high cholesterol

HPLC/DMS-MS/MS:

Liquid chromatography/differential ion mobility spectrometry tandem mass spectrometry

HUVEC:

Human umbilical vein endothelial cells

IL-1β:

Interleukin-1β

IL-6:

Interleukin-6

LTP:

Long-term potentiation

MAFLD:

Metabolic dysfunction-associated fatty liver disease

MMP:

Matrix metalloproteinases

MMP2:

Matrix metalloproteinase 2

MMP9:

Matrix metalloproteinase 9

MS:

Multiple sclerosis

NFL:

Neurofilament protein

NFTs:

Neurofibrillary tangles

NMDAR1:

N-methyl-d-asperate receptor 1

OIS:

Oncogene-induced senescence

Ops:

Oligodendrocyte progenitors

PD:

Parkinson’s disease

PDD:

Parkinson’s disease dementia

PSD-95:

Postsynaptic density-95 kDa

ROS:

Oxygen species

SAMP8:

Senescence-accelerated prone mouse strain 8

SAMR1:

Senescence-accelerated mouse resistant 1

SASP:

Senescence-associated secretory phenotype

SHRs:

Spontaneously hypertensive rats

SIRT1:

Sirtuin 1

SYN:

Synaptophysin

TMA:

Trimethylamine

TMAO:

Trimethylamine N-oxide

TNF-α:

Tumor necrosis factor-α

VSMC:

Vascular smooth muscle cell

WKY:

Wistar-Kyoto

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Funding

The present study was supported by the National Natural Science Foundation of China (Grants 81671166, 81571151, 81601140, and 81641039), and Fundamental Research Funds for the Central Universities of Central South University (grant 2021zzts1033, 2021zzts1029).

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Authors and Affiliations

  1. Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People’s Republic of China

    Lin Zhang, Fang Yu & Jian Xia

  2. Clinical Research Center for Cerebrovascular Disease of Hunan Province, Central South University, Changsha, Hunan, China

    Jian Xia

  3. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China

    Jian Xia

  4. Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China

    Lin Zhang

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  1. Lin Zhang
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  2. Fang Yu
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They were involved in writing the paper and had final approval of the submitted and published versions.

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Correspondence to Jian Xia.

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Zhang, L., Yu, F. & Xia, J. Trimethylamine N-oxide: role in cell senescence and age-related diseases. Eur J Nutr 62, 525–541 (2023). https://doi.org/10.1007/s00394-022-03011-w

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  • DOI: https://doi.org/10.1007/s00394-022-03011-w

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