Abstract

Metformin is an oral anti-diabetic used as first-line therapy for type 2 diabetes. Because benefits of metformin extend beyond diabetes to other age-related pathology, and because its effect on gene expression profiles resembles that of caloric restriction, metformin has a potential as an anti-aging intervention and may soon be assessed as an intervention to extend healthspan. However, beneficial actions of metformin in the central nervous system have not been clearly established. The current study examined the effect of chronic oral metformin treatment on motor and cognitive function when initiated in young, middle-aged, or old male mice. C57BL/6 mice aged 4, 11, or 22 months were randomly assigned to either a metformin group (2 mg/ml in drinking water) or a control group. The mice were monitored weekly for body weight, as well as food and water intake and a battery of behavioral tests for motor, cognitive and visual function was initiated after the first month of treatment. Liver, hippocampus and cortex were collected at the end of the study to assess redox homeostasis. Overall, metformin supplementation in male mice failed to affect blood glucose, body weights and redox homeostasis at any age. It also had no beneficial effect on age-related declines in psychomotor, cognitive or sensory functions. However, metformin treatment had a deleterious effect on spatial memory and visual acuity, and reduced SOD activity in brain regions. These data confirm that metformin treatment may be associated with deleterious effect resulting from the action of metformin on the central nervous system.

Highlights

  • Metformin is an oral anti-diabetic used as first-line therapy for type 2 diabetes

  • The major findings of the study were that metformin supplementation in male mice: (i) failed to affect blood glucose levels, body weight or redox homeostasis at any age and did not yield beneficial effects against ageimpaired psychomotor, cognitive or sensory functions (ii) had an age-dependent deleterious effect on spatial memory and visual acuity, and (iii) reduced Superoxide dismutase (SOD) activity in cortex and hippocampus of old mice

  • Metformin was without notable effect on food intake, body weight, water intake, and blood glucose levels

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Summary

Introduction

Metformin is an oral anti-diabetic used as first-line therapy for type 2 diabetes. Because benefits of metformin extend beyond diabetes to other age-related pathology, and because its effect on gene expression profiles resembles that of caloric restriction, metformin has a potential as an anti-aging intervention and may soon be assessed as an intervention to extend healthspan. The activity of superoxide dismutase and enzymes involved in the homeostasis of glutathione were measured in liver, cortex and hippocampus to determine whether age and metformin treatment had any effect.

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