Nicotinamide Adenine Dinucleotide in Aging Biology: Potential Applications and Many Unknowns.

IF 22 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Endocrine reviews Pub Date : 2023-11-09 DOI:10.1210/endrev/bnad019
Shalender Bhasin, Douglas Seals, Marie Migaud, Nicolas Musi, Joseph A Baur
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Abstract

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.

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烟酰胺腺嘌呤二核苷酸在衰老生物学中的潜在应用和许多未知。
最近的研究揭示了NAD+在细胞能量生成、氧化还原反应中的广泛作用,并在调节健康寿命和衰老的信号通路中作为底物或共底物。本综述对NAD+前体治疗年龄相关疾病的临床药理学、临床前和临床证据进行了批判性评估,特别关注心脏代谢疾病,并讨论了当前知识的空白。NAD+水平在整个生命过程中下降;年龄相关的NAD+生物利用度下降被认为是许多年龄相关疾病的一个因素。通过给药NAD+前体提高模式生物的NAD+水平可改善糖脂代谢;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;改善心力衰竭模型左心室功能;减轻脑血管和神经退行性疾病;延长了健康寿命。早期的人体研究表明,口服NAD+前体可以安全地提高血液和某些组织中的NAD+水平,并表明在预防非黑色素皮肤癌、适度降低血压和改善肥胖或超重老年人的血脂水平方面有好处;预防高危患者肾损伤;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。我们认为,这些早期发现为充分有力的随机试验提供了理论依据,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有效性。
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来源期刊
Endocrine reviews
Endocrine reviews 医学-内分泌学与代谢
CiteScore
42.00
自引率
1.00%
发文量
29
期刊介绍: Endocrine Reviews, published bimonthly, features concise timely reviews updating key mechanistic and clinical concepts, alongside comprehensive, authoritative articles covering both experimental and clinical endocrinology themes. The journal considers topics informing clinical practice based on emerging and established evidence from clinical research. It also reviews advances in endocrine science stemming from studies in cell biology, immunology, pharmacology, genetics, molecular biology, neuroscience, reproductive medicine, and pediatric endocrinology.
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