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Sex Matters in Aging. The Canagliflozin Story
Jackson Wezeman1, Warren Ladiges1
1Department of Comparative Medicine, School of Medicine, University of Washington, Seattle, WA, USA.
Abstract:
A promising and novel approach for identifying anti-aging therapeutics has been the repurposing of clinically approved and readily available drugs in mice. Canagliflozin, a clinically approved safe, and effective drug for type 2 diabetic patients, was recently shown to robustly retard age-related lesions in male mice but less so in female mice. While this type of sex disparity is often seen in the field of aging, it does represent a dilemma of not knowing the cause or how translationally relevant the sex differences would be in older humans treated with Canagliflozin. Thoughtful and mechanistic investigations are needed to understand why these differences are present and whether they can be eliminated by new drugs or drug combinations. Success in using repurposed drugs for aging intervention studies in humans will depend on preclinical research to uncover pathways that can be targeted for the benefit of both sexes.
Insights
Repurposing drugs like Canagliflozin shows promise for anti-aging interventions. However, observed sex differences in efficacy require further investigation for human translation and equitable benefits.
Area of Science:
- Gerontology
- Pharmacology
- Drug Repurposing
Background:
- Drug repurposing offers a novel strategy for identifying anti-aging therapeutics.
- Canagliflozin, a type 2 diabetes drug, has shown efficacy in retarding age-related lesions in male mice, but less so in females.
Purpose of the Study:
- To investigate the mechanistic basis for sex disparities in Canagliflozin's anti-aging effects.
- To determine the translational relevance of these sex differences for older humans.
Main Methods:
- Preclinical studies in mice utilizing Canagliflozin.
- Mechanistic investigations into observed sex-based differences.
Main Results:
- Canagliflozin demonstrated robust retardation of age-related lesions in male mice.
- A significant sex disparity was observed, with less pronounced effects in female mice.
Conclusions:
- Understanding the cause of sex differences is crucial for developing broadly effective anti-aging therapies.
- Further research is needed to identify targeted pathways for equitable benefits in both sexes.
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