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Functional and multi-omic aging rejuvenation with GLP-1R agonism

ABSTRACT: Identifying readily implementable methods that can effectively counteract aging is urgently needed for tackling age-related degenerative disorders. Here, we conducted functional assessments and deep molecular phenotyping in the aging mouse to demonstrate that glucagon-like peptide-1 receptor agonist (GLP-1RA) treatment attenuates body-wide age-related changes. In male mice treated with a GLP-1RA from 11 months of age for 30 weeks, we observed improvements in physical and cognitive performance, alongside age-counteracting effects that are prominently evident at multiple omic levels. These span the transcriptomes and DNA methylomes of various tissues, organs and circulating white blood cells, as well as the plasma metabolome. Importantly, the beneficial effects are specific to the aging mice, not young adults, and are achieved with a relatively low dosage of GLP-1RA which has a negligible impact on food consumption and body weight. In older mice treated with a GLP-1RA from 18 months of age for 13 weeks, the molecular rejuvenation effects are even more prominent and generally dependent on hypothalamic GLP-1R, pointing to a brain-body axis of aging modulation. We benchmarked the GLP-1RA age-counteracting effects against those of mTOR inhibition, a well-established anti-aging intervention, observing a strong resemblance across the two strategies. Our findings have broad implications for understanding the mechanistic basis of the clinically observed pleiotropic effects of GLP-1RAs, the design of intervention trials for age-related diseases, and the development of anti-aging-based therapeutics.

ORGANISM(S): Mus musculus Homo sapiens Rattus Macaca mulatta

PROVIDER: GSE279437 | GEO | 2025/11/20

REPOSITORIES: GEO

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Functional and multi-omic aging rejuvenation with GLP-1R agonism [bulk RNA-seq]

Project description:Identifying readily implementable methods that can effectively counteract aging is urgently needed for tackling age-related degenerative disorders. Here, we conducted functional assessments and deep molecular phenotyping in the aging mouse to demonstrate that glucagon-like peptide-1 receptor agonist (GLP-1RA) treatment attenuates body-wide age-related changes. In male mice treated with a GLP-1RA from 11 months of age for 30 weeks, we observed improvements in physical and cognitive performance, alongside age-counteracting effects that are prominently evident at multiple omic levels. These span the transcriptomes and DNA methylomes of various tissues, organs and circulating white blood cells, as well as the plasma metabolome. Importantly, the beneficial effects are specific to the aging mice, not young adults, and are achieved with a relatively low dosage of GLP-1RA which has a negligible impact on food consumption and body weight. In older mice treated with a GLP-1RA from 18 months of age for 13 weeks, the molecular rejuvenation effects are even more prominent and generally dependent on hypothalamic GLP-1R, pointing to a brain-body axis of aging modulation. We benchmarked the GLP-1RA age-counteracting effects against those of mTOR inhibition, a well-established anti-aging intervention, observing a strong resemblance across the two strategies. Our findings have broad implications for understanding the mechanistic basis of the clinically observed pleiotropic effects of GLP-1RAs, the design of intervention trials for age-related diseases, and the development of anti-aging-based therapeutics.

2025-11-20 | GSE280382 | GEO

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Microarray was used to detect the expression of lncRNAs and mRNAs in INS-1 cells treated with GLP-1RA Geniposide for 24 hours.

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2020-10-06 | GSE138744 | GEO

Effects of semaglutide on the gut microbiota of high-fat diet-fed mice lacking GLP-1Rs in T cells

Project description:Gut intraepithelial lymphocytes (IELs) are one of the few immune cell populations in the body that expresses glucagon-like 1 receptors (GLP-1R). To test the potential effects of GLP-1 on the gut microbiota through the gut IEL GLP-1R, we performed 16s rRNA seq on the DNA isolated from the fecal pellet of Lck-Cre; Glp1rfl/fl mice (Glp1rTcell-/-) or controls (Glp1rTcell+/+) fed a high-fat diet (HFD) for 12 weeks followed by 1 week of HFD plus semaglutide (10 ug/kg) or vehicle treatment. Fecal pellets from a group of age-matched, sex-matched control mice were included as a chow control group.

2022-08-29 | GSE202452 | GEO

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