NAD+代谢与肌少症：从分子机制到潜在干预策略的研究进展

NAD+ Metabolism and Sarcopenia: Research Progress from Molecular Mechanisms to Potential Intervention Strategies

摘要: 肌少症作为一种与衰老密切相关的骨骼肌质量与功能进行性下降综合征，已成为全球公共卫生的重大挑战。NAD+作为细胞能量代谢和多种信号通路的核心辅因子，其水平随年龄增长而显著下降，被认为是驱动肌肉衰老和功能衰退的关键因素。当前研究揭示了NAD+耗竭通过损害线粒体功能、扰乱蛋白质稳态、加剧细胞衰老和慢性炎症等多条分子通路，最终导致肌少症。针对这一机制，提升肌肉NAD+水平被视为潜在的治疗策略。本文系统总结了通过补充NAD+前体(如NMN、NR)、调节其合成酶或激活下游效应因子(如sirtuins)来改善肌肉质量和功能的临床前与临床研究进展，并对该领域面临的挑战、未来研究方向及转化应用前景进行了展望。

Abstract: Sarcopenia, a syndrome characterized by progressive decline in skeletal muscle mass and function closely associated with aging, has emerged as a major global public health challenge. NAD+, a core co-factor in cellular energy metabolism and multiple signaling pathways, significantly decreases with age and is considered a key driver of muscle aging and functional decline. Current research has revealed that NAD+ depletion leads to sarcopenia through multiple molecular pathways, including impairing mitochondrial function, disrupting protein homeostasis, accelerating cellular senescence, and exacerbating chronic inflammation. In response to this mechanism, enhancing muscle NAD+ levels is regarded as a potential therapeutic strategy. This article systematically summarizes the preclinical and clinical research progress in improving muscle mass and function by supplementing NAD+ precursors (such as NMN, NR), regulating its synthetase, or activating downstream effectors (such as sirtuins), and provides an outlook on the challenges, future research directions, and translational application prospects in this field.