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- Title
Systemic GLP-1R agonist treatment reverses mouse glial and neurovascular cell transcriptomic aging signatures in a genome-wide manner.
- Authors
Li, Zhongqi; Chen, Xinyi; Vong, Joaquim S. L.; Zhao, Lei; Huang, Junzhe; Yan, Leo Y. C.; Ip, Bonaventure; Wing, Yun Kwok; Lai, Hei-Ming; Mok, Vincent C. T.; Ko, Ho
- Abstract
Pharmacological reversal of brain aging is a long-sought yet challenging strategy for the prevention and treatment of age-related neurodegeneration, due to the diverse cell types and complex cellular pathways impacted by the aging process. Here, we report the genome-wide reversal of transcriptomic aging signatures in multiple major brain cell types, including glial and mural cells, by systemic glucagon-like peptide-1 receptor (GLP-1R) agonist (GLP-1RA) treatment. The age-related expression changes reversed by GLP-1RA encompass both shared and cell type-specific functional pathways that are implicated in aging and neurodegeneration. Concomitantly, Alzheimer's disease (AD)-associated transcriptomic signature in microglia that arises from aging is reduced. These results show the feasibility of reversing brain aging by pharmacological means, provide mechanistic insights into the neurological benefits of GLP-1RAs, and imply that GLP-1R agonism may be a generally applicable pharmacological intervention for patients at risk of age-related neurodegeneration. Li, Chen, Vong, Zhao et al. show that glucagon-like peptide-1 receptor agonist reverses transcriptomic aging signatures in mouse glial and neurovascular cells. This study suggests that glucagon-like peptide-1 receptor agonists may be considered as a therapeutic option for patients at risk of age-related neurodegeneration.
- Subjects
NEURODEGENERATION; TRANSCRIPTOMES; GLUCAGON-like peptide-1 receptor; NEUROGLIA; MICROGLIA
- Publication
Communications Biology, 2021, Vol 4, Issue 1, p1
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-021-02208-9