ArticleAging cell2022
Neuroprotective effects of Canagliflozin: Lessons from aged genetically diverse UM-HET3 mice.
Article in Aging cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Effect of antidiabetic drugs in Alzheimer´s disease: a systematic review of preclinical and clinical studies.Molecular neurodegeneration · 2025Pooled it
- Sex-stratified immune patterns across the canine lifespan and short-term responses to geroprotective interventions.Biogerontology · 2026Article
- Lifelong restriction of dietary valine has sex-specific benefits for health and lifespan in mice.Nature aging · 2026Article
- SGLT2 Inhibitors in Alzheimer's Disease: Biochemical Insights and Therapeutic Potential.International journal of molecular sciences · 2026Review
- Acarbose improves cognitive function in a mouse model of normal aging but not Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
- Mechanistic Links Between the Gut Microbiome and Longevity Therapeutics.Biomedicines · 2026Review
- Canagliflozin Reprograms the Aging Hippocampus in Genetically Diverse UM-HET3 Mice and Attenuates Alzheimer's-Like Pathology.Aging cell · 2025Article
- Targeting Neurodegeneration with SGLT2is: From Molecular Mechanisms to Clinical Implications.Molecular neurobiology · 2025Review
- Lifelong restriction of dietary valine has sex-specific benefits for health and lifespan in mice.bioRxiv : the preprint server for biology · 2025Article
- Canagliflozin treatment prevents follicular exhaustion and attenuates hallmarks of ovarian aging in genetically heterogenous mice.GeroScience · 2025Article
- Downregulation of the NF-κB protein p65 is a shared phenotype among most anti-aging interventions.GeroScience · 2025Article
- SGLT2 inhibitors as a novel senotherapeutic approach.npj aging · 2025Review
- Canagliflozin-Induced Adaptive Metabolism in Bone.Diabetes · 2025Article
- Genetic diversity leads to differential inflammatory responses to cigarette smoke in mice.Physiological reports · 2025Article
- The Promising Potency of Sodium-Glucose Cotransporter 2 Inhibitors in the Prevention of and as Treatment for Cognitive Impairment Among Type 2 Diabetes Patients.Biomedicines · 2024Review
- Lifespan effects in male UM-HET3 mice treated with sodium thiosulfate, 16-hydroxyestriol, and late-start canagliflozin.GeroScience · 2024Article
- Hypothalamic sex-specific metabolic shift by canagliflozin during aging.GeroScience · 2024Article
- Canagliflozin Mitigated Cognitive Impairment in Streptozotocin-Induced Sporadic Alzheimer's Disease in Mice: Role of AMPK/SIRT-1 Signaling Pathway in Modulating Neuroinflammation.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Article
- Early Life Interventions: Impact on Aging and Longevity.Aging and disease · 2024Review
- Narrative Review of Immunomodulatory and Anti-inflammatory Effects of Sodium-Glucose Cotransporter 2 Inhibitors: Unveiling Novel Therapeutic Frontiers.Kidney international reports · 2024Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
The aging brain is characterized by progressive increases in neuroinflammation and central insulin resistance, which contribute to neurodegenerative diseases and cognitive impairment. Recently, the Interventions Testing Program demonstrated that the anti-diabetes drug, Canagliflozin (Cana), a sodium-glucose transporter 2 inhibitor, led to lower fasting glucose and improved glucose tolerance in both sexes, but extended median lifespan by 14% in male mice only. Here, we show that Cana treatment significantly improved central insulin sensitivity in the hypothalamus and the hippocampus of 30-month-old male mice. Aged males produce more robust neuroimmune responses than aged females. Remarkably, Cana-treated male and female mice showed significant reductions in age-associated hypothalamic gliosis with a decrease in inflammatory cytokine production by microglia. However, in the hippocampus, Cana reduced microgliosis and astrogliosis in males, but not in female mice. The decrease in microgliosis was partially correlated with reduced phosphorylation of S6 kinase in microglia of Cana-treated aged male, but not female mice. Thus, Cana treatment improved insulin responsiveness in aged male mice. Furthermore, Cana treatment improved exploratory and locomotor activity of 30-month-old male but not female mice. Taken together, we demonstrate the sex-specific neuroprotective effects of Cana treatment, suggesting its application for the potential treatment of neurodegenerative diseases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.