Body fat not always bad

Jun 11 2004

With the threat of an obesity crisis looming, a study led by UCL researchers reveals today that fat tissue isn’t always the enemy. Reporting in the journal Science they show that a molecular signalling pathway in fat tissue is an important mediator in extending lifespan.

The study, conducted on one of scientists’ favourite model organisms - the fruit fly - found that reducing activity of the insulin/insulin-like growth factor (IIS) signalling pathway in fat tissue of adults extended life by up to 50 per cent.

Previously it has been shown that reducing the activity of the IIS pathway extends lifespan in fruit flies, mice and the worm C. elegans. But the cellular processes that determine longevity were not understood.

Results suggest the system that governs longevity evolved in a precursor of all three species and is likely to be conserved in humans.

Professor Linda Partridge of UCL’s Department of Biology, and senior author of the study, says:

“Basically, we are learning that nearly everything in biology is highly conserved. For years biologists studying ageing were convinced that it just happened and there wouldn't be genes that controlled it - you just wore out. But it became apparent independent of weight or size, some animals live much longer than others.

“Researchers became intrigued that on average a mouse lives for two years, a canary for 13 and a bat for 50 yet these species are all around the same size and warm blooded. A tortoise lives for up to one hundred years, but humans live for only 75. This suggests there must be a genetic determinant of the rate of ageing and these regulatory mechanisms can be set differently in different species. All we have to do is crack the code to reset the clock and our research takes this a step closer.”

The possibility of extending life span has preoccupied scientists for many years. Leading theories include the idea that eating less slows down the progressive damage caused by free radicals that are released when oxygen is used to breakdown fats and carbohydrates. But another theory is that calorie restriction does something critical to the insulin-signalling pathway that helps regulate how glucose is used by the body.

Dr Maria Giannakou of UCL’s Department of Biology, who led the study, explains:

“Studies in rats have shown restricting diet doubles lifespan but the pay off is reduced fertility. Elsewhere, groups have looked at mutations such as the DAF-2 gene in C. elegans, which can also double life span or reduce fertility depending on what stage in life the gene is interfered with.

“DAF-2 encodes the worms’ equivalent of the human insulin receptor and as such form part of the IIS pathway. As animals on restricted diets are far less likely to get diabetes and related disorders, this suggests that genes involved in glucose metabolism might be linked to the genes involved in ageing.”

Previous studies have shown reducing DAF-2 function during development affects only fertility, but in adulthood reducing function affects only lifespan. The researchers concluded that the two effects influenced different parts of the IIS pathway and their affects could be isolated.

Efforts focussed on a key target in the IIS pathway in the fruit fly, dFOXO. Known as a transcription factor, it helps activate and regulate genes.

They found that increasing levels of the transcription factor dFOXO in the fat cells of female fruit flies from the onset of adulthood increased lifespan by between 20 and 50 per cent and reduced fertility by 50 per cent. But no effect was observed in male flies.

“The functions of fruit fly fat include many of the metabolic activities of mammalian liver and fat storage. In mice deletion of insulin receptors in white fat cells results in a lean long living adult. Together this suggests that fat tissue is crucial in extending lifespan by altering the IIS pathway,” said Dr Giannakou.

“Further work needs to be done to determine why there is a different affect in both sexes,” added Professor Partridge.

“It could be because females are more influenced by food and its consequences. They make things – eggs, babies, and need a lot of nutrients for this. Males tend to move around a lot - to find females and persuade them to mate, and need less nutrients to make things. But this is just speculation.”

The study was funded by the Wellcome Trust and the Biotechnology and Biological Science Research Council.