Liver key to extending life (ABC News in Science)

Monday, 18 March 2002 Anna Salleh – ABC Science Online

Holes in blood vessel walls deplete: Sample A is from the blood vessel of the liver of a young rat; Sample B is from an old rat and has few holes. (Pic: D. Le Couteur)

An Australian expert argues that the liver is a neglected key in anti-ageing research.

Professor David Le Couteur, of the Centre for Education and Research in Ageing at Concord Hospital, presented his case at a symposium at Sydney University on Saturday.

There are many wonderful things about getting older, said Dr Le Couteur, a geriatrician with a background in clinical pharmacology and toxicology.

"Your mortgage is paid off, your children have moved out, you're not embarrassed about who you are, and you have the benefit of wisdom and resilience," he said.

"It would be fine if it wasn't for dementia, arthritis, heart disease, cancer, and pneumonia. This is why we are actively investigating new ways to prevent age-related disease."

Professor Le Couteur said that many age-related illnesses were caused by toxins and fats and that this is where his interest in the liver came from.

The liver's role in the body is to process blood coming from the gut by absorbing nutrients, metabolising fats, and processing toxins.

"Previous to our research, the liver was not thought to change much during ageing, except for shrinking in size," he said.

However Professor Le Couteur and colleague Allan McLean of the National Ageing Research Institute in Melbourne have discovered that as the liver ages, its blood vessels also change.

The blood vessels in a healthy liver have tiny holes in their walls to allow blood going from the gut into the liver to be processed.

Professor Le Couteur and team have found that in rats, baboons, and humans these tiny holes seem to clog up or disappear as the liver ages.

"This means that fats and toxins can't get processed properly," he said. "And it explains a lot of problems."

For example, he said, the fats involved in atherosclerosis — the build-up on blood vessel walls — float around in the blood because they are unable to be processed properly in the liver.

In an article due to appear in medical journal The Lancet next month, Professor Le Couteur argues that the age-related increase in atherosclerosis is due to these age-related changes in the liver.

Previous research has shown that toxins such as alcohol and bacteria-derived toxins damage the holes in the blood vessels, but this is the first time this type of process has been related to diseases of ageing.

"Rather than simply using drugs to treat Alzheimer's and heart disease, we could be using a broader range of interventions targeted at the liver instead," Professor Le Couteur said.

His team is exploring avenues such as reducing food intake, using antioxidants designed to work specifically in the liver at time of digestion, improving blood flow to the liver, and using substances that return the healthy holes in liver blood vessels.

Interestingly, alcohol is one such substance that helps to punch holes in the liver blood vessels — which could explain the so-called 'wine paradox'. Alcohol in moderation is beneficial to health but too much is bad.

Professor Le Couteur's research has been mainly funded by the National Health and Medical Research Council.

http://www.abc.net.au/science/articles/2002/03/18/505524.htm