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Clinical perspectives and concerns of metformin as an anti-aging drug.

ABSTRACT: As percentages of elderly people rise in many societies, age-related diseases have become more prevalent than ever. Research interests have been shifting to delaying age-related diseases by delaying or reversing aging itself. We use metformin as an entry point to talk about the important molecular and genetic longevity-regulating mechanisms that have been extensively studied with it. Then we review a number of observational studies, animal studies, and clinical trials to reflect the clinical potentials of the mechanisms in lifespan extension, cardiovascular diseases, tumors, and neurodegeneration. Finally, we highlight remaining concerns that are related to metformin and future anti-aging research.

SUBMITTER: Wang C

PROVIDER: S-EPMC7771567 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Clinical perspectives and concerns of metformin as an anti-aging drug.

Wang Chuyao C Chen Bangwei B Feng Qian Q Nie Chao C Li Tao T

Aging medicine (Milton (N.S.W)) 20201201 4

As percentages of elderly people rise in many societies, age-related diseases have become more prevalent than ever. Research interests have been shifting to delaying age-related diseases by delaying or reversing aging itself. We use metformin as an entry point to talk about the important molecular and genetic longevity-regulating mechanisms that have been extensively studied with it. Then we review a number of observational studies, animal studies, and clinical trials to reflect the clinical pot ...[more]

PMID: 33392433

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Project description:The numerous beneficial health outcomes associated with the use of metformin to treat patients with type 2 diabetes (T2DM), together with data from pre-clinical studies in animals including the nematode, C. elegans, and mice have prompted investigations into whether metformin has therapeutic utility as an anti-aging drug that may also extend lifespan. Indeed, clinical trials, including the MILES (Metformin In Longevity Study) and TAME (Targeting Aging with Metformin), have been designed to assess the potential benefits of metformin as an anti-aging drug. Preliminary analysis of results from MILES indicate that metformin may induce anti-aging transcriptional changes; however it remains controversial as to whether metformin is protective in those subjects free of disease. Furthermore, despite clinical use for over 60 years as an anti-diabetic drug, the cellular mechanisms by which metformin exerts either its actions remain unclear. In this review, we have critically evaluated the literature that has investigated the effects of metformin on aging, healthspan and lifespan in humans as well as other species. In preparing this review, particular attention has been placed on the strength and reproducibility of data and quality of the study protocols with respect to the pharmacokinetic and pharmacodynamic properties of metformin. We conclude that despite data in support of anti-aging benefits, the evidence that metformin increases lifespan remains controversial. However, via its ability to reduce early mortality associated with various diseases, including diabetes, cardiovascular disease, cognitive decline and cancer, metformin can improve healthspan thereby extending the period of life spent in good health. Based on the available evidence we conclude that the beneficial effects of metformin on aging and healthspan are primarily indirect via its effects on cellular metabolism and result from its anti-hyperglycemic action, enhancing insulin sensitivity, reduction of oxidative stress and protective effects on the endothelium and vascular function.

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Clinical perspectives and concerns of metformin as an anti-aging drug.

Publications

Clinical perspectives and concerns of metformin as an anti-aging drug.

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