US scientists have found a gene that appears to be involved in extending the lifespan of laboratory worms when they are kept on a severely calorie restricted diet. It is possible that the equivalent gene in humans may have the same effect.
The study is published in the journal Nature.
Since the 1930s scientists have demonstrated that mice and other organisms kept on a near starvation, calorie restricted, diet live about 40 per cent longer than those who are well-fed.
These studies have shown that cutting calorie intake to 60 per cent of normal while making sure the diet has all the right amounts of vitamins, minerals and other essential nutrients prolongs life and reduces the risk of cancer, diabetes, and heart disease while delaying the onset of brain degenerative illnesses in many laboratory animals like mice, dogs and monkeys.
However, no study has yet shown whether the lifespan-enhancing benefit of a calorie restricted diet found in laboratory animals also apply to humans.
Some people, believe that it does, and follow a strict low calorie regimen every day; for instance the Californian group called the Calorie Restriction Society live on half the recommended 2,000 calories a day.
A restricted diet makes the body respond in a way that is different to when metabolism and growth slow down, and appears to be triggered by a genetic programme that is sensitive to nutrient intake.
But exactly how this happens was a mystery until scientists from the Salk Institute for Biological Studies in La Jolla, California, looked specifically at how certain genes behave under these near starvation conditions in a nematode worm called Caenorhabditis elegans.
Why the interest in a nematode worm? Because a gene in question, PHA-4, has an equivalent in mammals like mice and humans: the “Foxa” family of genes.
In the nematode worm, previous studies have shown that PHA-4 helps to grow the foregut. And the PHA-4 equivalent in mammals, the Foxa family of genes: Foxa1, Foxa2 and Foxa3 are also active in early development. But the Foxa genes also have a role in later life: they help to regulate glucagon, which, unlike insulin, increases blood sugar and maintains the body’s energy balance, particularly under calorie-restricted conditions.
The new contribution this study makes is to discover that PHA-4 also has a role in later life, in the adult C. elegans nematode worm, namely that it appears to be extending the lifespan of the worm under diet-restricted conditions independently of other genetic ageing pathways.
Two experiments in the study were particularly significant in confirming the role of PHA-4. When it was knocked out, the lifespan-enhancing effect disappeared in the calorie-restricted worms. And when the scientists caused it to be over-expressed, the lifespan-enhancing effect was increased.
This showed that PHA-4 acts independently of other longevity pathways.
Until now, only one other gene, sir-2, has been shown to play a role in prolonging lifespan under calorie restricted conditions. Increasing sir-2 protein extends the lifespan of yeast, worms and flies. But when it is removed, it only makes the lifespan-enhancing response to calorie restriction happen in yeast; the other organisms, including worms, are not affected.
Dr Andrew Dillin, who led the study and is associate professor in the Molecular and Cell Biology Laboratory at the Salk Institute said:
“We know three distinct pathways that affect longevity: insulin/IGF signaling, calorie restriction, and the mitochondrial electron transport chain pathway, yet it is still not clear where sir-2 fits in. It seems to meddle with more than one pathway.”
But, he explained, “PHA-4 is specific for calorie restriction as it does not affect the other pathways.”
The new question that arises as a result of this study is this:
If PHA-4 has an indenpendent way of extending lifespan that is triggered by a restricted diet, is it possible that its mammalian relative, the Foxa gene family, has a similar effect in mammals? The hope is that further studies will find this, or something like this, to be the case.
“After 72 years of not knowing how calorie restriction works, we finally have genetic evidence to unravel the underlying molecular program required for increased longevity in response to calorie restriction.”
Speculating on the possible benefits of this research, the scientists suggest this opens the door to developing drugs that imitate the effect of a calorie restricted diet on extending longevity without people having to endure near starvation.
“PHA-4/Foxa mediates diet-restriction-induced longevity of C. elegans.”
Siler H. Panowski, Suzanne Wolff, Hugo Aguilaniu, Jenni Durieux and Andrew Dillin.
Nature advance online publication 2 May 2007.
doi:10.1038/nature05837
Written by: Catharine Paddock
Writer: Medical News Today