Highlights

  • Metformin supplementation improves the firing rates of neurons in the visual cortex of aged mice. 
  • Supplementation with metformin improves visual cortex information processing in aged mice. 
  • Metformin increases the level of proteins involved in inhibiting the electrical activity of the brain, which may explain the above effects. 

Not all age-related vision deficits involve the eye and retina. Vision deficits can also stem from alterations in the visual cortex—the visual processing region of the brain. Studies show that impairments in visual processing precede impairments in cognitive processing, yet many scientists focus on the cognitive aspects of brain aging. 

This neglect is not the case with a group of researchers in China, Liu and colleagues, who, in a new study published in Frontiers in Aging Neuroscience, examined the visual cortex of aged mice. Remarkably, they found that the diabetes drug metformin prevented the visual processing deficits observed in aged mice. The findings suggest that metformin may counteract certain age-related vision deficits. 

Metformin Improves Age-Related Neuronal Firing Alterations 

Liu and colleagues first examined how aging affects visual processing by comparing young and aged mice. The young mice were 8 weeks old, which is roughly equivalent to a 17-year-old human. The aged mice were 12 months old, which is roughly equivalent to a 44-year-old human. To measure visual cortex activity, an electrode was surgically placed into the visual cortex, and electrical signals were recorded in response to various visual stimuli. 

(Liu et al., 2025) Recording Electrical Signals from the Visual Cortex. An electrode was surgically implanted into the visual cortex of mice. In turn, electrical activity, in response to various visual stimuli, was recorded. 

When we visualize something, the neurons in our visual cortex fire electrical spikes, and this firing can occur at different rates. When we visualize something simple, like a blank screen, the firing rate is slower than when we visualize something more complex, such as a moving pattern. Furthermore, spontaneous spikes will fire even when looking at a blank screen or other less complex visuals. 

Mice are the same, and the researchers found that aged mice, when looking at a blank screen, exhibited higher spontaneous firing rates than young mice. Firing rates were also higher in aged mice in response to visualizing moving patterns. These findings suggest that aging leads to increased neuronal firing in the visual cortex. What’s more, additional measurements suggested that the neurons of aged mice encode sensory information less effectively.  

The Effects of Metformin

Metformin is a type 2 diabetes drug that has been repurposed as an investigational health and longevity drug. It’s considered an anti-aging drug because it has been shown to prolong the lifespan of several model organisms. Moreover, it’s been shown to have neuroprotective effects against various neurodegenerative disorders, such as Parkinson’s and Alzheimer’s disease. 

To test its effect on the visual cortex, the researchers fed 250 mg/kg of metformin to aged mice. This dose corresponds to 1200 mg/day, which is the dose given to type 2 diabetes patients, according to the researchers. Incredibly, the neurons of aged mice fed metformin exhibited firing rates and sensory encoding similar to those of young mice. These findings reveal that metformin may prevent age-related alterations in visual cortex neuronal firing.   

(Liu et al., 2025) Metformin Prevents Neuronal Hyperactivity in Visual Cortex. Aged mice (red) exhibit higher electrical spike firing rates than young mice (green) when visualizing a blank screen (left) or a moving pattern (right). However, metformin (blue) prevents this from occurring.

Metformin Improves Visual Cortex Information Processing  

The full breadth of visual information processing doesn’t occur at the level of individual neurons, but involves networks of neurons. It follows that while single neurons transmit information in the form of electrical spikes, populations of neurons carry and encode more information and better represent the activity of whole brain regions. 

Liu and colleagues measured information processing from increasingly larger populations of visual cortex neurons in mice. Compared to young mice, aged mice exhibited lower information processing, aligning with age-related visual perception deficits. However, metformin was shown not only to prevent, but also to improve these information processing deficits. 

(Liu et al., 2025) Metformin Improves Visual Cortex Information Processing. Aged mice (red) exhibit lower information processing than young mice (green), particularly with larger populations of neurons. However, aged mice treated with metformin (blue) exhibit even higher levels of information processing than young mice.  

Metformin Increases Major Electrical Inhibition Proteins 

The level of electrical activity in our brain is largely determined by excitatory and inhibitory neurotransmitters. While excitatory neurotransmitters increase firing rates, inhibitory neurotransmitters decrease firing rates. The primary inhibitory neurotransmitter of our brain is called GABA (gamma-aminobutyric acid). When GABA binds to GABA receptors, it inhibits the firing of neurons. Alcohol also binds GABA receptors, producing alcohol’s sedative effects. 

Reduced GABA activity is associated with neuronal hyperactivity and deficits in information processing in the visual cortex. Metformin readily crosses the blood-brain barrier and has been shown to increase GABA receptor-related components. It has also been shown to restore GABA levels in rats with diabetic epilepsy. For these reasons, Liu and colleagues examined the protein levels of GABA-related components. 

The researchers found that metformin increased two GABA-related proteins called GAD67 and gephyrin in aged mice. GAD67 is a crucial enzyme involved in the synthesis of the GABA neurotransmitter, suggesting that metformin increases GABA synthesis. Gephyrin is a scaffolding protein that clusters and organizes GABA receptors, suggesting that metformin improves GABA signaling. Notably, even young mice did not exhibit high levels of these proteins. 

(Liu et al., 2025) Metformin Elevates GABA Signaling Proteins. Compared to young (green) and aged (red) mice, metformin-treated aged mice (blue) exhibit higher levels of GAD67 (left) and gephyrin (right), which are critical proteins involved in GABAergic signaling.

Together, the findings of Liu and colleagues suggest that metformin improves visual cortex function by increasing GABA neurotransmitter signaling. The improvements in visual cortex activity and increase in GABA-related proteins went beyond that of young mice, raising the question of whether metformin can improve visual processing in healthy brains. However, there is currently a lack of evidence supporting this idea. 

Taking Metformin to Counteract Age-Related Vision Deficits 

Age-related deficits in visual processing are by no means benign, as they contribute to vehicle accidents. Alterations to the visual cortex may also contribute to falls and lower quality of life for older adults. Thus, taking metformin to improve visual processing may promote health and longevity by enhancing quality of life and preventing lethal accidents. However, there is little evidence showing that improving visual cortex information processing with metformin leads to better vision. 

Still, metformin does show promise in other aspects of age-related vision complications, particularly age-related macular degeneration (AMD). AMD does not involve the visual cortex, but the macula, which is part of the eye. A recent study showed that metformin supplementation was associated with a lower risk of AMD in older adults with diabetes. More studies are needed to determine whether metformin supports the prevention of AMD in healthy individuals without diabetes.

Ultimately, metformin seems to be beneficial for diabetes patients, who have high glucose levels, but whether metformin is beneficial to non-diabetics will require more research. It’s possible that reducing carbohydrate intake can reap similar benefits to metformin, particularly when it comes to reducing neuronal hyperactivity. The ketogenic diet, which involves very little carbohydrate, is known to treat epilepsy in this manner.