METFORMIN AS A PROMISING ANTI-AGING AGENT IN THE TREATMENT OF OSTEOARTHRITIS

Tsvetoslav Georgiev, P. Kabakchieva
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Abstract

Osteoarthritis (OA) is traditionally considered an age-related disease. Therefore, repurposing drugs with the potential to reduce cell senescence is a justified therapeutic strategy. Such is the case of metformin, the most widely used antidiabetic medicine with well-known pharmacokinetics, acceptable toxicity, and beneficial metabolic effects. Metformin could significantly impact processes associated with aging and OA such as cellular senescence, infammaging, mitochondrial dysfunction and impaired nutrient sensing. The aim of the present narrative review is to unveil the potential of metformin to modify disease course in light of aging osteoarthritic joints. The drug has pleiotropic effects on chondrocyte and extracellular matrix metabolism and may provide through AMPK-dependent and -independent pathways a meaningful improvement of OA. Mostly preclinical and retrospective cohort studies have shown that metformin exposure could lead to the regulation of cartilage homeostasis, symptomatic relief of pain and postpone surgery for those suffering from OA. Randomized control trials are warranted to justify the preliminary expectations.
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二甲双胍作为一种有前景的抗衰老剂治疗骨关节炎
骨关节炎(OA)传统上被认为是一种与年龄有关的疾病。因此,重新利用具有减少细胞衰老潜力的药物是一种合理的治疗策略。二甲双胍就是这样的例子,它是最广泛使用的抗糖尿病药物,具有众所周知的药代动力学、可接受的毒性和有益的代谢作用。二甲双胍可以显著影响与衰老和OA相关的过程,如细胞衰老、炎症、线粒体功能障碍和营养感知受损。目前的叙述回顾的目的是揭示二甲双胍的潜力,以改变老化的骨关节炎关节的疾病进程。该药物对软骨细胞和细胞外基质代谢具有多效性作用,并可能通过ampk依赖性和非依赖性途径对OA有意义的改善。大多数临床前和回顾性队列研究表明,二甲双胍暴露可能导致软骨稳态调节,疼痛症状缓解,并推迟OA患者的手术。随机对照试验可以证明初步预期的正确性。
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