CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism.
CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism.
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DOI：
10.1016/j.cmet.2016.05.006
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发表时间：
2016-06-14
期刊：
影响因子：
29
通讯作者：
Chini EN
中科院分区：
文献类型：
--
作者：
Camacho-Pereira J;Tarragó MG;Chini CCS;Nin V;Escande C;Warner GM;Puranik AS;Schoon RA;Reid JM;Galina A;Chini EN
烟酰胺腺嘌呤二核苷酸（NAD）水平随着年龄的增长而下降，并与年龄相关的代谢下降有关。迄今为止，NAD与年龄相关的减少的机制尚未阐明。在这里，我们证明了NADase CD38的表达和活性随着年龄的增长而增加，并且CD38是年龄相关的NAD下降和线粒体功能障碍所必需的，其途径至少部分由SIRT3活性调节介导。我们还发现CD38是参与体内NAD前体烟酰胺单核苷酸（NMN）降解的主要酶，这表明CD38在调节衰老和代谢性疾病的NAD替代疗法中起关键作用。CD38/NADase在衰老过程中增加，导致NAD下降和随后的线粒体功能障碍。为什么NAD水平会随着年龄的增长而下降？Camacho等人现在发现，NADase CD38的表达增加以sirt3依赖的方式导致老年小鼠NAD下降和线粒体功能障碍。CD38还代谢NAD前体NMN，并调节体内对NAD替代治疗的反应。
Nicotinamide Adenine Dinucleotide (NAD) levels decrease during aging, and are involved in age-related metabolic decline. To date, the mechanism responsible for the age-related reduction in NAD has not been elucidated. Here we demonstrate that expression and activity of the NADase CD38 increase with aging and that CD38 is required for the age-related NAD decline and mitochondrial dysfunction via a pathway mediated at least in part by regulation of SIRT3 activity. We also identified CD38 as the main enzyme involved in the degradation of the NAD precursor nicotinamide mononucleotide (NMN) in vivo, indicating that CD38 has a key role in the modulation of NAD-replacement therapy for aging and metabolic diseases. CD38/NADase increases during aging, and causes NAD decline and subsequent mitochondrial dysfunction. Why do NAD levels decrease with age? Camacho et al. now reveal that increased expression of the NADase CD38 is responsible for NAD decline and mitochondrial dysfunction in older mice in a SIRT3-dependent manner. CD38 also metabolizes the NAD precursor NMN and modulates the response to NAD-replacement therapy in vivo.