Recent research has unveiled an expansive role of NAD+ in cellular energy generation, redox reactions, and as a substrate or cosubstrate in signaling pathways that regulate health span and aging. This review provides a critical appraisal of the clinical pharmacology and the preclinical and clinical evidence for therapeutic effects of NAD+ precursors for age-related conditions, with a particular focus on cardiometabolic disorders, and discusses gaps in current knowledge. NAD+ levels decrease throughout life; age-related decline in NAD+ bioavailability has been postulated to be a contributor to many age-related diseases. Raising NAD+ levels in model organisms by administration of NAD+ precursors improves glucose and lipid metabolism; attenuates diet-induced weight gain, diabetes, diabetic kidney disease, and hepatic steatosis; reduces endothelial dysfunction; protects heart from ischemic injury; improves left ventricular function in models of heart failure; attenuates cerebrovascular and neurodegenerative disorders; and increases health span. Early human studies show that NAD+ levels can be raised safely in blood and some tissues by oral NAD+ precursors and suggest benefit in preventing nonmelanotic skin cancer, modestly reducing blood pressure and improving lipid profile in older adults with obesity or overweight; preventing kidney injury in at-risk patients; and suppressing inflammation in Parkinson disease and SARS-CoV-2 infection. Clinical pharmacology, metabolism, and therapeutic mechanisms of NAD+ precursors remain incompletely understood. We suggest that these early findings provide the rationale for adequately powered randomized trials to evaluate the efficacy of NAD+ augmentation as a therapeutic strategy to prevent and treat metabolic disorders and age-related conditions.

中文翻译：

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烟酰胺腺嘌呤二核苷酸在衰老生物学中：潜在应用和许多未知数。


最近的研究揭示了 NAD+ 在细胞能量产生、氧化还原反应中的广泛作用，以及作为调节健康持续时间和衰老的信号通路中的底物或共底物。本综述对临床药理学以及 NAD+ 前体对年龄相关疾病的治疗效果的临床前和临床证据进行了批判性评估，特别关注心脏代谢紊乱，并讨论了当前知识的空白。NAD+ 水平在一生中不断下降;据推测，与年龄相关的 NAD+ 生物利用度下降是导致许多与年龄相关的疾病的原因。通过施用 NAD + 前体提高模式生物中的 NAD + 水平可改善葡萄糖和脂质代谢;减轻饮食引起的体重增加、糖尿病、糖尿病肾病和肝脂肪变性;减少内皮功能障碍;保护心脏免受缺血性损伤;改善心力衰竭模型中的左心室功能;减轻脑血管和神经退行性疾病;并增加生命值。早期人类研究表明，口服 NAD+ 前体可以安全地提高血液和某些组织中的 NAD+ 水平，并表明有助于预防非黑色素性皮肤癌、适度降低血压和改善肥胖或超重老年人的血脂状况;预防高危患者的肾损伤;以及抑制帕金森病和 SARS-CoV-2 感染的炎症。NAD+ 前体的临床药理学、代谢和治疗机制仍不完全清楚。 我们建议这些早期发现为具有足够把握度的随机试验提供了基本原理，以评估 NAD+ 增强作为预防和治疗代谢紊乱和年龄相关疾病的治疗策略的疗效。