本期节目邀请了神经学家Dena Dubal教授，深入探讨了长寿因子Klotho的奥秘，包括其在体内的形成和分布、影响其水平的因素（如压力和运动）以及其对认知功能和整体脑健康的影响。Dena分享了激动人心的动物模型研究成果，展示了Klotho在治疗神经退行性疾病方面的潜力，以及其对器官健康和疾病预防的更广泛意义。她对人类未来研究以及Klotho在预防和治疗阿尔茨海默病方面的潜力抱有乐观态度。

🤔 **Klotho的生物学特性：**Klotho是一种在肾脏中产生的蛋白质，具有抗氧化、抗炎和促进细胞生长等多种生物学功能。随着年龄的增长，Klotho的水平会下降，这与衰老和多种疾病的发生密切相关。研究表明，压力、运动、饮食等因素都会影响Klotho的水平。

🧠 **Klotho对脑健康的影响：**研究表明，Klotho水平较高的人群，认知功能更佳，患阿尔茨海默病的风险也更低。在动物模型中，Klotho的补充可以改善认知功能，减缓神经元死亡，并保护大脑免受损伤。

🧬 **Klotho与基因变异：**人类的KL-VS基因变异会影响Klotho的水平。携带KL-VS基因变异的人群，Klotho水平较低，患阿尔茨海默病的风险也更高。

💊 **Klotho的治疗潜力：**目前，科学家们正在研究Klotho的治疗潜力，希望将其应用于治疗阿尔茨海默病、帕金森病等神经退行性疾病。

💪 **Klotho对整体健康的影响：**研究表明，Klotho水平与寿命、心血管健康、骨骼健康等密切相关。Klotho水平较高的人群，整体健康状况更佳，患慢性疾病的风险也更低。

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Dena Dubal is a physician-scientist and professor of neurology at UCSF whose work focuses on mechanisms of longevity and brain resilience. In this episode, Dena delves into the intricacies of the longevity factor klotho: its formation and distribution in the body, the factors such as stress and exercise that impact its levels, and its profound impact on cognitive function and overall brain health. Dena shares insights from exciting research in animal models showing the potential of klotho in treating neurodegenerative diseases as well as its broader implications for organ health and disease prevention. She concludes with an optimistic outlook for future research in humans and the potential of klotho for the prevention and treatment of Alzheimer’s disease.

Disclosure: Peter is an investor in Jocasta Neuroscience, a company working to develop klotho as a therapy for people with Alzheimer’s disease.

We discuss:

Dena’s fascination with aging and how she came to study klotho [3:30]; Biological properties of klotho: production, regulation, decline with age, and factors influencing its levels [11:45]; Potential benefits of klotho on brain health [22:00]; The relationship between soluble klotho protein, platelet factors, and cognitive enhancement [33:45]; The role of platelet factor 4 (PF4) and it’s interaction with GluN2B in mediating cognitive enhancement [46:45]; Benefits of klotho observed in a mouse model of Parkinson’s disease [55:45]; Benefits of klotho observed in a mouse model of Alzheimer’s disease [1:03:00]; Promising results of klotho in primate models, and the importance of finding an appropriate therapeutic dose before moving to human trials [1:08:00]; Speculating why a single klotho injection has such long-lasting effects [1:25:30]; Potential cognitive benefits of klotho in humans, the impact of the KL-VS genetic variant on klotho levels, and the need for human trials to confirm these effects [1:27:45]; The interaction between the KL-VS genetic variant and APOE4 and how it impacts risk of Alzheimer’s disease [1:34:45]; The significance of klotho levels: studies linking lower levels to increased mortality and the broader implications for organ health and disease prevention [1:47:15]; Measuring klotho levels and determining an individual’s KL-VS status [1:52:15]; The promising potential of klotho for Alzheimer’s disease treatment, and the importance of philanthropy for funding research [1:58:00]; and More.

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