本期节目邀请到衰老研究领域的权威专家Nir Barzilai教授，他分享了关于延长寿命和健康寿命的最新研究成果。节目探讨了百岁老人的基因特征、影响长寿的重要途径以及如何从百岁老人身上学习延缓衰老的方法。此外，Barzilai教授还深入探讨了二甲双胍作为延长寿命工具的潜力，包括其对运动的影响以及未来研究方向。

🤔 **百岁老人的基因秘密**：研究表明，百岁老人拥有独特的基因变异，例如APOE e2、Lp(a)、Klotho和CETP等，这些变异与长寿密切相关。此外，高TSH水平也与长寿有关。这些研究结果为理解衰老机制和开发延缓衰老的药物提供了宝贵的线索。

💪 **长寿的生物学途径**：节目中讨论了影响长寿的重要生物学途径，包括生长激素和IGF-1信号通路、线粒体功能和细胞自噬等。研究表明，调节这些途径可以延缓衰老进程，提高健康寿命。

💊 **二甲双胍的潜力**：二甲双胍作为一种常见的糖尿病药物，近年来被发现具有延缓衰老的潜力。节目中讨论了二甲双胍在动物模型中的研究结果以及正在进行的TAME试验，该试验旨在评估二甲双胍对人类健康寿命的影响。TAME试验的数据将为未来研究提供宝贵的参考，例如用于识别二甲双胍治疗的最佳人群。

🏃 **二甲双胍与运动**：研究表明，二甲双胍可以增强运动效果，尤其是在力量训练和心血管训练方面。然而，二甲双胍对不同人群的影响可能存在差异，因此需要进一步研究确定其最佳应用范围。

🧬 **未来研究方向**：节目中还探讨了其他延缓衰老的潜在方法，例如NAD前体。未来研究将重点关注寻找有效的生物标志物，以识别能够从延缓衰老治疗中获益的人群，并开发更有效的延缓衰老药物。

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Nir Barzilai, Director of the Institute for Aging Research at the Albert Einstein College of Medicine, is back for his third appearance on The Drive. In this episode, Nir divulges insights into lifespan and healthspan through the lens of his extensive research on centenarians as well as the latest from the TAME trial (Targeting/Taming Aging with Metformin), a multi-center study investigating the concept that the multi-morbidities of aging can be delayed in humans. He discusses common gene variants found in centenarians, important pathways for longevity, and ultimately what we can learn from centenarians about extending lifespan while also trying to improve healthspan. Additionally, Nir goes into depth on metformin as a longevity tool for humans, including studies with positive and negative results. He discusses the impact metformin can have on exercise for both strength training and cardiovascular training, as well as future research facilitated by data from the TAME Trial. He also touches on epigenetic clocks and concludes with his take on the usefulness of NAD precursors as a potential gero-protective agent.

We discuss:

• Insights from genetic studies of centenarians and twins [3:00];
• Genes with protective variants that aid longevity [13:00];
• The relationship between growth hormone and IGF-1 [22:45];
• Use of growth hormone as a longevity tool [34:00];
• Longevity genotypes: the role of APOE e2, Lp(a), Klotho, and CETP [41:45];
• The correlation between high TSH and longevity [46:30];
• Important pathways for longevity [52:00];
• Insights from centenarian studies, nature vs. nurture, and more [59:00];
• The contraction of morbidity that comes with improved healthspan [1:08:00];
• Defining healthspan [1:13:13];
• Unique perspectives and positive attitudes of centenarians [1:17:30];
• Lessons to take away from centenarians [1:24:00];
• Metformin overview: history, studies, and potential for gero-protection [1:28:45];
• The TAME trial (Targeting Aging with Metformin) [1:39:00];
• The challenge of studying metformin in animals models [1:46:45];
• How data from the TAME trial could provide insights into biomarkers of aging and facilitate a future study on proteomics [1:53:30];
• The search for biomarkers to identify who can benefit from treatment [2:00:30];
• The impact of metformin on exercise, and finding the right indication for the use of metformin [2:10:30];
• Are NAD precursors geroprotective? [2:21:30]; and
• More.

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