Sex Matters in Aging. The Canagliflozin Story.

Jackson Wezeman, Warren Ladiges
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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.

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性与衰老有关。卡格列净的故事。
鉴别抗衰老疗法的一种有前途的新方法是在小鼠身上重新利用临床批准和现成的药物。Canagliflozin是一种临床批准的安全有效的治疗2型糖尿病患者的药物,最近在雄性小鼠中显示出强大的延缓年龄相关病变的作用,但在雌性小鼠中效果较差。虽然这种类型的性别差异在衰老领域经常看到,但它确实代表了一个困境,即不知道原因,也不知道在使用卡格列净治疗的老年人中,性别差异的翻译相关性如何。需要深思熟虑和机械的研究来理解为什么这些差异存在,以及它们是否可以被新药或药物组合消除。在人类衰老干预研究中成功地使用重新用途的药物将取决于临床前研究,以发现可以针对两性利益的途径。
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