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烟酰胺腺嘌呤二核苷酸在衰老和缺血条件下成为治疗靶点。

Nicotinamide adenine dinucleotide emerges as a therapeutic target in aging and ischemic conditions.

机构信息

Drug Applied Research Center, Department of Physiology, Tabriz University of Medical Sciences, Tabriz, Iran.

Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Biogerontology. 2019 Aug;20(4):381-395. doi: 10.1007/s10522-019-09805-6. Epub 2019 Mar 5.

Abstract

Nicotinamide adenine dinucleotide (NAD) has been described as central coenzyme of redox reactions and is a key regulator of stress resistance and longevity. Aging is a multifactorial and irreversible process that is characterized by a gradual diminution in physiological functions in an organism over time, leading to development of age-associated pathologies and eventually increasing the probability of death. Ischemia is the lack of nutritive blood flow that causes damage and mortality that mostly occurs in various organs during aging. During the process of aging and related ischemic conditions, NAD levels decline and lead to nuclear and mitochondrial dysfunctions, resulting in age-related pathologies. The majority of studies have shown that restoring of NAD using supplementation with intermediates such as nicotinamide mononucleotide and nicotinamide riboside can be a valuable strategy for recovery of ischemic injury and age-associated defects. This review summarizes the molecular mechanisms responsible for the reduction in NAD levels during ischemic disorders and aging, as well as a particular focus is given to the recent progress in the understanding of NAD precursor's effects on aging and ischemia.

摘要

烟酰胺腺嘌呤二核苷酸(NAD)被描述为氧化还原反应的中心辅酶,是应激抵抗和长寿的关键调节剂。衰老是一个多因素和不可逆转的过程,其特征是随着时间的推移,生物体的生理功能逐渐减弱,导致与年龄相关的病理发生,并最终增加死亡的概率。缺血是指营养血液供应不足,导致损伤和死亡,这种情况在衰老过程中主要发生在各种器官中。在衰老和相关的缺血情况下,NAD 水平下降,导致核和线粒体功能障碍,从而导致与年龄相关的病理。大多数研究表明,使用烟酰胺单核苷酸和烟酰胺核苷等中间体补充 NAD 可以成为恢复缺血损伤和与年龄相关缺陷的有价值的策略。本综述总结了在缺血性疾病和衰老过程中导致 NAD 水平降低的分子机制,并特别关注对 NAD 前体对衰老和缺血影响的最新认识。

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