Systemic GLP-1R agonist treatment reverses mouse glial and neurovascular cell transcriptomic aging signatures in a genome-wide manner

• DOI: 10.1038/s42003-021-02208-9
• Publication Date: 2021-06-02T10:08:04Z
• Authors: Zhongqi Li; Xinyi Chen; Joaquim S. L. Vong; Lei Zhao; Junzhe Huang; Leo Y. C. Yan; Bonaventure Ip; Yun Kwok Wing; Hei-Ming Lai; Vincent C. T. Mok; Ho Ko
• Keywords: TREM2; Aging brain; Cell type

Abstract Pharmacological reversal of brain aging is a long-sought yet challenging strategy for the prevention and treatment age-related neurodegeneration, due to diverse cell types complex cellular pathways impacted by process. Here, we report genome-wide transcriptomic signatures in multiple major types, including glial mural cells, systemic glucagon-like peptide-1 receptor (GLP-1R) agonist (GLP-1RA) treatment. The expression changes reversed GLP-1RA encompass both shared type-specific functional that are implicated neurodegeneration. Concomitantly, Alzheimer’s disease (AD)-associated signature microglia arises from reduced. These results show feasibility reversing pharmacological means, provide mechanistic insights into neurological benefits GLP-1RAs, imply GLP-1R agonism may be generally applicable intervention patients at risk