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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\u2019s 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.<\/jats:p>","DOI":"10.1038\/s42003-021-02208-9","type":"journal-article","created":{"date-parts":[[2021,6,2]],"date-time":"2021-06-02T06:08:04Z","timestamp":1622614084000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Systemic GLP-1R agonist treatment reverses mouse glial and neurovascular cell transcriptomic aging signatures in a genome-wide manner"],"prefix":"10.1038","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2554-9334","authenticated-orcid":false,"given":"Zhongqi","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5859-2008","authenticated-orcid":false,"given":"Joaquim S. 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Z.L., X.C., J.S.L.V., L.Z., J.H., L.Y.C.Y., H.M.L., V.C.T.M., and H.K. are inventors on the patent. Exenatide used in the study was provided by AstraZeneca Hong Kong Limited. AstraZeneca Hong Kong Limited had otherwise no role in the funding, design, execution or data interpretation of the study. All other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"656"}}