Ikeno Yuji
Barshop Institute for Longevity and Aging Studies, San Antonio, TX 78229, USA.
Department of Pathology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Aging Pathobiol Ther. 2021;3(2):17-19. doi: 10.31491/apt.2021.06.056. Epub 2021 Jun 29.
After the discovery of thioredoxin as a reductant for many important enzymes in the early 1960s, biological roles of thioredoxin in pathophysiology have been examined using various species and experimental models, e.g., yeast, invertebrates, rodents, and humans. A large number of studies demonstrated that thioredoxin plays an essential role to maintain a reduced cellular environment and possesses many beneficial effects by maintaining cellular/organ functions and against diseases. However, an important question that remains to be answered is whether thioredoxin could attenuate aging by reducing oxidative damage and changing cellular redox state, which alters redox-sensitive signaling pathways. To address this important question, we have been conducting aging studies with transgenic and knockout mice, and transgenic rats to examine whether the upregulation or downregulation of thioredoxin alters lifespan and age-related pathology. Aging studies conducted by our laboratory and others revealed that the roles of thioredoxin on pathophysiology seem to be more complex than our initial expectations as a potential magic bullet to solve the issues with age. Recent studies indicate that thioredoxin could have both beneficial and potentially deleterious effects on aging and age-related diseases. To critically evaluate the biological effects of thioredoxin on aging and age-related diseases, studies require further consideration to assess additional factors, e.g. levels of thioredoxin in different cellular compartments, different effects in each cell/tissue/organ, physiological aging vs. pathology, and/or at different life stages.
20世纪60年代初发现硫氧还蛋白是许多重要酶的还原剂后，人们利用各种物种和实验模型，如酵母、无脊椎动物、啮齿动物和人类，研究了硫氧还蛋白在病理生理学中的生物学作用。大量研究表明，硫氧还蛋白在维持细胞内还原环境方面起着至关重要的作用，并通过维持细胞/器官功能和抵抗疾病而具有许多有益作用。然而，一个有待回答的重要问题是，硫氧还蛋白是否可以通过减少氧化损伤和改变细胞氧化还原状态来延缓衰老，而细胞氧化还原状态的改变会影响氧化还原敏感信号通路。为了解决这个重要问题，我们一直在用转基因和基因敲除小鼠以及转基因大鼠进行衰老研究，以检验硫氧还蛋白的上调或下调是否会改变寿命和与年龄相关的病理变化。我们实验室和其他机构进行的衰老研究表明，硫氧还蛋白在病理生理学中的作用似乎比我们最初期望的作为解决衰老问题的潜在神奇药物更为复杂。最近的研究表明，硫氧还蛋白可能对衰老和与年龄相关的疾病既有有益影响，也有潜在的有害影响。为了严格评估硫氧还蛋白对衰老和与年龄相关疾病的生物学效应，研究需要进一步考虑评估其他因素，例如不同细胞区室中硫氧还蛋白的水平、在每个细胞/组织/器官中的不同作用、生理衰老与病理变化，和/或在不同生命阶段的情况。
