Promise of metformin for preventing age-related cognitive dysfunction  

作　　者：Leelavathi N.Madhu Maheedhar Kodali Ashok K.Shetty 

机构地区：[1]Institute for Regenerative Medicine,Department of Molecular and Cellular Medicine,Texas A&M University College of Medicine,College Station,TX,USA

出　　处：《Neural Regeneration Research》2022年第3期503-507,共5页中国神经再生研究（英文版）

基　　金：supported by grants from the National Institutes of Health (No.1R01NS106907,to AKS);the Department of Defense (Nos.W81XWH-17-1-0447 and W81XWH-19-1-0548,to AKS)。

摘　　要：The expanded lifespan of people,while a positive advance,has also amplified the prevalence of age-related disorders,which include mild cognitive impairment,dementia,and Alzheimer's disease.Therefore,competent therapies that could improve the healthspan of people have great significance.Some of the dietary and pharmacological approaches that augment the lifespan could also preserve improved cognitive function in old age.Metformin,a drug widely used for treating diabetes,is one such candidate that could alleviate age-related cognitive dysfunction.However,the possible use of metformin to alleviate age-related cognitive dysfunction has met with conflicting results in human and animal studies.While most clinical studies have suggested the promise of metformin to maintain better cognitive function and reduce the risk for developing dementia and Alzheimer's disease in aged diabetic people,its efficacy in the nondiabetic population is still unclear.Moreover,a previous animal model study implied that metformin could adversely affect cognitive function in the aged.However,a recent animal study using multiple behavioral tests has reported that metformin treatment in late middle age improved cognitive function in old age.The study also revealed that cognitionenhancing effects of metformin in aged animals were associated with the activation of the energy regulator adenosine monophosphate-activated protein kinase,diminished neuroinflammation,inhibition of the mammalian target of rapamycin signaling,and augmented autophagy in the hippocampus.The proficiency of metformin to facilitate these favorable modifications in the aged hippocampus likely underlies its positive effect on cognitive function.Nonetheless,additional studies probing the outcomes of different doses and durations of metformin treatment at specific windows in the middle and old age across sex in nondiabetic and non-obese prototypes are required to substantiate the promise of metformin to maintain better cognitive function in old age.

关 键 词：activated microglia aging AUTOPHAGY cognitive dysfunction memory METFORMIN mTOR signaling NEUROINFLAMMATION 

分 类 号：R749.1[医药卫生—神经病学与精神病学]