Metformin is an oral prescription drug approved by the US FDA in 1994 to treat raised blood glucose in people with type 2 diabetes.
Metformin is also used to manage polycystic ovary syndrome (a hormonal disorder which affects up to 20% of women), while recent studies have suggested other health benefits may include anti-cancer properties, combating obesity, and helping protect the cardiovascular and nervous system.
Now some experts suggest metformin may have anti-ageing effects, and even extend lifespan – leading to a trial being set up by the American Federation for Ageing Research. The Targeting Ageing with Metformin (TAME) Trial will enrol 3,000 individuals aged 65- 79 in a series of nationwide, 6-year clinical trials at 14 leading research institutions across the USA. The trials will test whether metformin delays development or progression of age- related chronic diseases, such as heart disease, cancer and dementia.
Some studies in animals have suggested metformin can increase lifespan. A UK study published in the journal Cell reported nematode worms given metformin at 25, 50 and 100 millimoles (mM) concentration increased mean lifespan by 18%, 36% and 3%.
A US study published in Nature Communications reported mice given metformin at 0.1% wet weight in diet starting in middle age increased both lifespan and healthspan, but a higher dose (1% wet weight) was toxic.
And a Russian study published in the journal Aging reported female mice given metformin increased mean lifespan by 14% if started at 3 months; started later, the effect was much smaller, starting at 9 months increased lifespan by 6%, and at 15 months there was no increase; the drug also increased reproductive function and delayed tumour development.
However, a UK study published in PLoS One reported metformin given to fruit flies did not extend lifespan in male or female flies, and was toxic at higher doses.
In humans, a study published in Frontiers in Endocrinology reported metformin improves age-related diseases, such as type 2 diabetes, cardiovascular disease, and a study based on a Taiwanese cohort reported metformin may lead to extended lifespan.
Dr David Merrill, director of California’s Pacific Brain Health Center in Santa Monica explained to medicalnewstoday.com: ‘Metformin certainly lessens complications of type 2 diabetes, especially when combined with healthy carb-controlled diet and regular physical exercise. This will help reach the goal of ageing without chronic disease or disability. Metformin improves insulin sensitivity, promotes cellular repair, is anti-inflammatory and antioxidant. All these properties contribute to its anti-ageing effects.’
A UK study, published in Diabetes Care, reported metformin activates the AMP-activated protein kinase (AMPK) as well as autophagy (the process of cell recycling); both these may explain some of its anti-ageing properties.
Sebnem Unluisler, genetic engineer at the London Regenerative Institute, explained ‘metformin’s potential mechanisms for anti-ageing effects encompass its ability to influence critical processes associated with ageing. These include regulating nutrient sensing, maintaining proteostasis, improving mitochondrial function, modulating intercellular communication, preserving telomere length, stabilising the genome, impacting epigenetic modifications, attenuating stem cell depletion, and reducing cellular senescence.’
She noted that by controlling blood sugar, metformin helps prevent production of excess free radicals, thereby reducing oxidative stress and the age-related conditions it can cause. ‘By targeting these pathways, metformin has the potential to delay the onset or progression of age- related chronic diseases, including heart disease, cancer and dementia. These mechanisms may contribute to its observed benefits beyond glycemic control,’ she said.
Dr Tunc Tiryaki, consultant plastic surgeon at London’s Cadogan Clinic, told medicalnewstoday. com that metformin has also shown promise for facial bone and skin ageing. ‘Metformin’s mechanisms, such as stimulating bone formation and reducing resorption, offers the potential for maintaining facial bone density. As facial bones support the skin structure, this could translate to improved facial contours and reduced signs of ageing.’
Meanwhile the TAME trial aims to investigate whether metformin might work by targeting overall ageing, instead of treating age-related diseases individually. If the trial shows it does have anti-ageing effects, the organisers hope to gain FDA approval for the drug as an ‘indication’ for ageing – meaning metformin could be prescribed to treat ageing in people without type 2 diabetes or other indicated conditions such as PCOS.
