Delighted to share the latest paper from our team in Cell Metabolism (cell.com/cell-metabolism/ful…), which has been selected as the cover article for the upcoming December 2025 issue. In this study, we demonstrate that GLP-1R agonism (using the drug exenatide) confers body-wide multi-omic age-counteraction that rivals rapamycin, the mTOR inhibitor and benchmark anti-aging drug, in aging/aged male mice. Interestingly, we found that this is largely mediated through the hypothalamus in the brain. Our journey began eight years ago: Upon extensive literature review and in part inspired by the 2017 EXENATIDE-PD trial paper in Lancet, we first hypothesized that GLP-1RAs might have age-counteracting properties. We provided the first experimental evidence connecting aging and GLP-1 agonism in 2020 [nature.com/articles/s41467-0…], showing that exenatide treatment can potently counteract mouse brain vascular aging. We then demonstrated that such an effect extends to most gliovascular cell types in a companion paper in 2021 [nature.com/articles/s42003-0…]. Now, building on our prior works, we are delighted to offer the most direct experimental support to date for the growing discussion that this drug class holds significant anti-aging potential inferred from the expanding list of clinical pleiotropic effects—a topic that was recently raised again by Dr. Lotte Bjerre Knudsen at ARDD 2025 and featured in Nature Biotechnology [nature.com/articles/s41587-0…]. Currently, our clinical team and collaborators are focused on leveraging the anti-aging and anti-neuroinflammatory mechanisms to test GLP-1RAs as treatments for cerebrovascular disorders (ClinicalTrials.gov: NCT05920889 [will be published very soon], NCT06788626 [getting close to the finish line], and NCT05356104 [will take another two years]). A huge thank you to our entire team and collaborators, editor and reviewers, and to Dr. Jennifer Ma for the cover art that perfectly captures the spirit of our work [stay tuned!], paying tribute to the scientists who made two remarkable discoveries: namely, the isolation of the first GLP-1RA exenatide from Gila monster venom, and rapamycin from Easter Island soil bacteria. Who would have thought that these two natural substances would converge on age-counteraction, at least in the aging mouse!