Press release

Study reveals how diabetes drug delays ageing in worms

A widely prescribed type 2 diabetes drug slows down the ageing process by mimicking the effects of dieting, according to a study published this week using worms to investigate how the drug works.

Following a calorie-restricted diet has been shown to improve health in later life and extend lifespan in several animals, from the simple worm to rhesus monkeys. The type 2 diabetes drug metformin has been found to have similar effects in animals, but until now it was not clear exactly how the drug delays the ageing process.

Researchers supported by the Wellcome Trust and Medical Research Council looked at the effects of metformin on C. elegans worms that were grown in the presence of E. coli bacteria, a relationship similar to that humans have with the 'healthy' bacteria in our gut. They found that the worms treated with metformin lived longer only when the E. coli strain they were cultured with was sensitive to the drug.

Dr Filipe Cabreiro from the Institute of Healthy Ageing at UCL, who led the research, explains: "Overall, treatment with metformin adds up to six days of life for the worm, which is equivalent to around a third of its normal lifespan. It seems to work by altering metabolism in the bacteria that live in the worm, which in turn limits the nutrients that are available to the worm host and has a similar effect to restricting the diet."

Bacteria living in the gut have an important role in helping the host organism to digest and extract nutrition from food. Defects in gut bacteria have been linked to metabolic diseases such as obesity, diabetes, inflammatory bowel disease and cancer. It has also been suggested that gut bacteria may have an impact on the ageing process, but this is the first study to suggest a mechanism for how this works.

The team used strains of E. coli with defects in genes that are linked to metabolism and tweaked the levels of nutrients available to tease out which metabolic pathways might be affected by the drug. They found that treatment with metformin disrupted the bacteria's ability to metabolise folate, a type of B-vitamin, and methionine, one of the building blocks of proteins. This limits the nutrients that are available to the worm and mimics the effects of dietary restriction to enable the worms to live longer.

When they added an excess of sugar to the diet, however, the team found that the life-extending effects of metformin were cancelled out. As the drug is used as a treatment for diabetes caused by elevated glucose levels in the blood, this finding is particularly relevant for understanding how the drug works in people.

Professor David Gems, who directed the study, said: "We don't know from this study whether metformin has any effect on human ageing. The more interesting finding is the suggestion that drugs that alter bacteria in the gut could give us a new way of treating or preventing metabolic diseases like obesity and diabetes."

Metformin is currently one of the most widely prescribed drugs and the findings should help to inform how it is used in patients.

The study was published today in the journal 'Cell'.

Reference

Cabreiro F et al. Metformin retards aging in C. elegans by altering microbial folate and methionine metabolism. Cell 2013 (epub ahead of print).

About UCL (University College London)

Founded in 1826, UCL was the first English university established after Oxford and Cambridge, the first to admit students regardless of race, class, religion or gender and the first to provide systematic teaching of law, architecture and medicine.

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About the Medical Research Council

Over the past century, the Medical Research Council has been at the forefront of scientific discovery to improve human health. Founded in 1913 to tackle tuberculosis, the MRC now invests taxpayers' money in some of the best medical research in the world across every area of health. Twenty-nine MRC-funded researchers have won Nobel prizes in a wide range of disciplines, and MRC scientists have been behind such diverse discoveries as vitamins, the structure of DNA and the link between smoking and cancer, as well as achievements such as pioneering the use of randomised controlled trials, the invention of MRI scanning, and the development of a group of antibodies used in the making of some of the most successful drugs ever developed.

Today, MRC-funded scientists tackle some of the greatest health problems facing humanity in the 21st century, from the rising tide of chronic diseases associated with ageing to the threats posed by rapidly mutating micro-organisms.

The MRC Centenary Timeline chronicles 100 years of life-changing discoveries and shows how our research has had a lasting influence on healthcare and wellbeing in the UK and globally, right up to the present day.

About the Wellcome Trust

The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust's breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests.