Medical Faculty, Department of Medical Biology and Genetics, Istanbul Aydin University, Istanbul, Turkey.
Cerrahpasa Faculty of Medicine, Department of Medical Biology, Istanbul University, Istanbul, Turkey.
Clin Exp Pharmacol Physiol. 2019 May;46(5):413-422. doi: 10.1111/1440-1681.13073. Epub 2019 Mar 12.
Ageing can be defined as the progressive failure of repair and maintenance systems with a consequent accumulation of cellular damage in nucleic acids, proteins, and lipids. These various types of damage promote ageing by driving cellular senescence and apoptosis. The nuclear factor-kappa B (NF-kB) pathway is one of the key mediators of ageing and this pathway is activated by genotoxic, oxidative and inflammatory stress, and regulates expression of cytokines, growth factors, and genes that regulate apoptosis, cell-cycle progression, and inflammation. Therefore, NF-kB is increased in a variety of tissues with ageing, thus the inhibition of NF-kB leads to delayed onset of ageing-related symptoms and pathologies such as diabetes, atherosclerosis, and cancer. Metformin is often used as an anti-diabetic medication in type 2 diabetes throughout the world and appears to be a potential anti-ageing agent. Owing to its antioxidant, anticancer, cardio-protective and anti-inflammatory properties, metformin has become a potential candidate drug, improving in the context of ageing and ageing-related diseases. An inappropriate NF-kB activation is associated with diseases and pathologic conditions which can impair the activity of genes involved in cell senescence, apoptosis, immunity, and inflammation. Metformin, inhibiting the expression of NF-kB gene, eliminates the susceptibility to common diseases. This review underlines the pleiotropic effects of metformin in ageing and different ageing-related diseases and attributes its effects to the modulation of NF-kB.
衰老是指修复和维护系统的逐渐失效，导致核酸、蛋白质和脂质中的细胞损伤不断积累。这些不同类型的损伤通过驱动细胞衰老和细胞凋亡来促进衰老。核因子-κB（NF-κB）途径是衰老的关键介质之一，该途径可被遗传毒性、氧化和炎症应激激活，并调节细胞因子、生长因子以及调节细胞凋亡、细胞周期进程和炎症的基因的表达。因此，NF-κB 在衰老的各种组织中增加，从而抑制 NF-κB 导致与衰老相关的症状和病理学的发病时间延迟，如糖尿病、动脉粥样硬化和癌症。二甲双胍在全世界常用于 2 型糖尿病的抗糖尿病药物，似乎是一种潜在的抗衰老剂。由于其抗氧化、抗癌、心脏保护和抗炎特性，二甲双胍已成为一种潜在的候选药物，可改善衰老和与衰老相关的疾病。NF-κB 的不适当激活与疾病和病理状况有关，这些疾病和病理状况会损害与细胞衰老、细胞凋亡、免疫和炎症相关的基因的活性。二甲双胍通过抑制 NF-κB 基因的表达，消除了对常见疾病的易感性。这篇综述强调了二甲双胍在衰老和不同与衰老相关的疾病中的多效性作用，并将其作用归因于 NF-κB 的调节。
