Lifespan effects in male UM-HET3 mice treated with sodium thiosulfate, 16-hydroxyestriol, and late-start canagliflozin
GeroScience, ISSN: 2509-2723, Vol: 46, Issue: 5, Page: 4657-4670
2024
- 3Citations
- 2Usage
- 3Captures
- 1Mentions
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Most Recent News
Findings in Sodium-Glucose Transporter 2 Inhibitors Reported from University of Michigan (Lifespan Effects In Male Um-het3 Mice Treated With Sodium Thiosulfate, 16-hydroxyestriol, and Late-start Canagliflozin)
2024 JUN 17 (NewsRx) -- By a News Reporter-Staff News Editor at NewsRx Drug Daily -- Current study results on Drugs and Therapies - Sodium-Glucose
Article Description
Genetically heterogeneous UM-HET3 mice born in 2020 were used to test possible lifespan effects of alpha-ketoglutarate (AKG), 2,4-dinitrophenol (DNP), hydralazine (HYD), nebivolol (NEBI), 16α-hydroxyestriol (OH_Est), and sodium thiosulfate (THIO), and to evaluate the effects of canagliflozin (Cana) when started at 16 months of age. OH_Est produced a 15% increase (p = 0.0001) in median lifespan in males but led to a significant (7%) decline in female lifespan. Cana, started at 16 months, also led to a significant increase (14%, p = 0.004) in males and a significant decline (6%, p = 0.03) in females. Cana given to mice at 6 months led, as in our previous study, to an increase in male lifespan without any change in female lifespan, suggesting that this agent may lead to female-specific late-life harm. We found that blood levels of Cana were approximately 20-fold higher in aged females than in young males, suggesting a possible mechanism for the sex-specific disparities in its effects. NEBI was also found to produce a female-specific decline (4%, p = 0.03) in lifespan. None of the other tested drugs provided a lifespan benefit in either sex. These data bring to 7 the list of ITP-tested drugs that induce at least a 10% lifespan increase in one or both sexes, add a fourth drug with demonstrated mid-life benefits on lifespan, and provide a testable hypothesis that might explain the sexual dimorphism in lifespan effects of the SGLT2 inhibitor Cana.
Bibliographic Details
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85193302581&origin=inward; http://dx.doi.org/10.1007/s11357-024-01176-2; http://www.ncbi.nlm.nih.gov/pubmed/38753230; https://link.springer.com/10.1007/s11357-024-01176-2; https://mouseion.jax.org/stfb2024/190; https://mouseion.jax.org/cgi/viewcontent.cgi?article=1199&context=stfb2024; https://dx.doi.org/10.1007/s11357-024-01176-2; https://link.springer.com/article/10.1007/s11357-024-01176-2
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