Nicotinamide adenine dinucleotide (NAD+) is an important natural molecule involved in fundamental biological processes, including the TCA cycle, OXPHOS, β-oxidation, and is a co-factor for proteins promoting healthy longevity. NAD+ depletion is associated with the hallmarks of ageing and may contribute to a wide range of age-related diseases including metabolic disorders, cancer, and neurodegenerative diseases. One of the central pathways by which NAD+ promotes healthy ageing is through regulation of mitochondrial homeostasis via mitochondrial biogenesis and the clearance of damaged mitochondria via mitophagy. Here, we highlight the contribution of the NAD+-mitophagy axis to ageing and age-related diseases, and evaluate how boosting NAD+ levels may emerge as a promising therapeutic strategy to counter ageing as well as neurodegenerative diseases including Alzheimer's disease. The potential use of artificial intelligence to understand the roles and molecular mechanisms of the NAD+-mitophagy axis in ageing is discussed, including possible applications in drug target identification and validation, compound screening and lead compound discovery, biomarker development, as well as efficacy and safety assessment. Advances in our understanding of the molecular and cellular roles of NAD+ in mitophagy will lead to novel approaches for facilitating healthy mitochondrial homoeostasis that may serve as a promising therapeutic strategy to counter ageing-associated pathologies and/or accelerated ageing.

中文翻译：

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NAD+-线粒体自噬轴在健康长寿和基于人工智能的临床应用中的作用。

烟酰胺腺嘌呤二核苷酸 (NAD+) 是一种重要的天然分子，参与 TCA 循环、OXPHOS、β-氧化等基本生物过程，并且是促进健康长寿的蛋白质的辅助因子。NAD+ 消耗与衰老标志相关，并可能导致多种与年龄相关的疾病，包括代谢紊乱、癌症和神经退行性疾病。NAD+ 促进健康衰老的核心途径之一是通过线粒体生物发生调节线粒体稳态，并通过线粒体自噬清除受损的线粒体。在这里，我们强调了 NAD+-线粒体自噬轴对衰老和年龄相关疾病的贡献，并评估了提高 NAD+ 水平如何成为对抗衰老以及包括阿尔茨海默氏病在内的神经退行性疾病的有前景的治疗策略。讨论了人工智能在了解 NAD+-线粒体自噬轴在衰老中的作用和分子机制方面的潜在用途，包括在药物靶标识别和验证、化合物筛选和先导化合物发现、生物标志物开发以及功效和安全性方面的可能应用评估。我们对 NAD+ 在线粒体自噬中的分子和细胞作用的理解的进展将带来促进健康线粒体稳态的新方法，这可能作为对抗衰老相关病理和/或加速衰老的有前途的治疗策略。