Systemic GLP-1R agonist treatment reverses mouse glial and neurovascular cell transcriptomic aging signatures in a genome-wide manner.
Zhongqi LiXinyi ChenJoaquim S L VongLei ZhaoJunzhe HuangLeo Y C YanBonaventure IpYun-Kwok WingHei-Ming LaiVincent Chung-Tong MokHo KoPublished in: Communications biology (2021)
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.
Keyphrases
- genome wide
- single cell
- dna methylation
- cell therapy
- rna seq
- randomized controlled trial
- resting state
- neuropathic pain
- stem cells
- functional connectivity
- gene expression
- poor prognosis
- cerebral ischemia
- inflammatory response
- systemic lupus erythematosus
- spinal cord injury
- cell death
- mesenchymal stem cells
- combination therapy
- binding protein
- blood brain barrier
- brain injury
- cell cycle arrest