Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ, USA.
Department of Neurology, University of Arizona, Tucson, AZ, USA; Evelyn F McKnight Brain institute and Center for Innovation in Brain Science, University of Arizona, Tucson, AZ, USA.
Free Radic Biol Med. 2019 Apr;134:702-707. doi: 10.1016/j.freeradbiomed.2019.01.016. Epub 2019 Jan 14.
NRF2, a transcription factor that has been deemed the master regulator of cellular redox homeostasis, declines with age. NRF2 transcriptionally upregulates genes that combat oxidative stress; therefore, loss of NRF2 allows oxidative stress to go unmitigated and drive the aging phenotype. Oxidative stress is a common theme among the key features associated with the aging process, collectively referred to as the "Hallmarks of Aging", as it disrupts proteostasis, alters genomic stability, and leads to cell death. In this review, we outline the role that oxidative stress and the reduction of NRF2 play in each of the Hallmarks of Aging, including how they contribute to the onset of neurodegenerative disorders, cancer, and other age-related pathologies.
NRF2 是一种被认为是细胞氧化还原稳态的主要调节因子的转录因子，其水平随着年龄的增长而下降。NRF2 转录上调了对抗氧化应激的基因；因此，NRF2 的缺失允许氧化应激不受抑制，并导致衰老表型。氧化应激是与衰老过程相关的关键特征之一，被称为“衰老的标志”，因为它破坏了蛋白质平衡，改变了基因组稳定性，并导致细胞死亡。在这篇综述中，我们概述了氧化应激和 NRF2 减少在衰老标志中的每一个中的作用，包括它们如何导致神经退行性疾病、癌症和其他与年龄相关的病理的发生。
