After analysing over 17,000 Dutch men and women, researchers found that those who drank seven or more cups of coffee a day were half as likely to develop the disease than those who drank two cups or less. The study was led by Rob van Dam while at the Dutch National Institute for Public Health and Environment in Bilthoven.

A spokesperson for Diabetes UK says that although they will not be advising people to drink seven cups of coffee a day at this stage, the results are surprising and dramatic.

The results may be welcome news for heavy coffee drinkers, as scientists have previously reported they are unusually sensitive to pain, prone to panic disorders and more likely to develop heart disease.

Magnesium and potassium

Type 2 diabetes is largely associated with sedentary lifestyles and used to appear mainly in older people. But as levels of obesity have increased in children, so too has the prevalence of the disease.

Sufferers experience increased blood glucose levels as their bodies either do not produce enough of the hormone insulin, which is responsible for the uptake of blood glucose by cells in the body, or their cells are less sensitive to insulin.

Caffeine is known to lower insulin sensitivity in the short term, so it would not be an obvious remedy for type 2 diabetes. But Van Dam points out that the long term affects of caffeine are unknown. Coffee contains other components, he notes, such as chlorogenic acid, magnesium and potassium, which could improve insulin sensitivity.

His team assessed the effects of drinking coffee over a period of seven years. The reduced risk for coffee drinkers was particularly surprising because risk factors for the disease, such as a less active lifestyle, were more common in that group.

Edwin Gale, at Bristol University, UK, thinks it is difficult to pin the reduced levels of type 2 diabetes on increased coffee consumption when behavioural forces could be at work. For example, heavy coffee drinkers might be less inclined to go see their doctors, he says.

Van Dam acknowledges that their findings need to be replicated and that the mechanism by which coffee may reduce the risk of type 2 diabetes needs elucidation. His team now plan to assess the affects of drinking decaffeinated coffee over long periods of time.

Journal reference: Lancet (vol 360, p 1477)

In previous work involving interfering with the gene, longer life was only achieved at the cost of a loss of ability to reproduce in C. elegans. “But knocking down the gene after the worms reach adulthood increases their life span without affecting their reproduction,” says Cynthia Kenyon at the University of California, San Francisco, who led the research.

The gene, called daf-2, is also found in fruit flies and mice, and Kenyon thinks it is possible that it is present in humans. Interfering with this gene in a similar way might also safely extend the human lifespan, she says.

But Tom Kirkwood, an expert on ageing at Newcastle University, UK, warns that the apparent absence of reproductive problems in the worms “does not mean longevity has come for free – the trade-off could be more subtle than this. When one looks for evidence of trade-offs, fertility is one of the things involved, but it’s not the only one.”

Independent pathways

Evolutionary biologists have long predicted that lifespan cannot be lengthened without a reproductive trade off. And in 1993, Kenyon discovered that knocking out the gene, called daf-2, at the point of hatching doubled the worm’s normal two-week lifespan. But they were unable to reproduce.

But now her team has shown that if daf-2 is switched off at the onset of adulthood, about four days after birth, the worms live twice as long as normal but reproduce normally.

What is more, if daf-2 is switched off when the worms hatch, then switched back on when they reach adulthood, the worms’ life span is not altered but the onset of their fertile period is delayed.

This shows that the daf-2 gene controls reproduction during the worm’s developmental phase and lifespan during its adult life. Since the two pathways are independent, there need not be a trade off between them at all, Kenyon argues.

Mario de Bono, who works with nematode worms at the MRC Laboratory of Molecular Biology in Cambridge, UK, welcomes the new findings. “The original daf-2 mutants were fine apart from their inhibited reproduction. If you can rescue this reproductive delay there’s no reason why the worms should exhibit other problems,” he says.

Journal reference: Science (vol 289, p 830)

Gene therapy replaces defective genes with healthy versions within the chromosome of patients’ cells, where that they can be replicated for a lifetime. Current methods of insertion use various viruses to ferry the genes, but the viruses insert them at random locations.

The risks of random insertion were highlighted at the start of October. A child who had received gene therapy for a rare immune disorder was revealed to have developed leukaemia as a direct result of the inserted gene landing inside a cancer-related gene.

The new method, developed by Michele Calos and colleagues at Stanford University Medical Center, California, delivers genes to specific locations within a chromosome, eliminating this risk. “This system seems to offer predictability and control over genes which simply isn’t possible with viral vectors”, Calos told żěè¶ĚĘÓƵ.

Simon Waddington, from the Gene Therapy Group at Imperial College, London, UK, says that not only are the risks of random insertion removed, but it also appears to be a very efficient method of gene therapy. Genes delivered randomly often insert into inactive parts of the genome, but the new method always inserts in active areas, he says: “So the integrated genes are sure to be expressed.”

Mix and match

The Stanford team copied a mechanism used by bacteriophages, viruses that infect bacteria. These make a special enzyme called “integrase” that cuts and inserts phage DNA into a specific site in the bacteria’s DNA.

It does so by identifying a stretch of phage DNA, known as the attP site, and binding it to a specific region on the bacterial chromosome known as the host attB site. There is also a mammalian version of the attP site, suggesting it could be used as a landing point for therapeutic genes.

The team injected mice with a haemophilia-related gene attached to an attB site. The gene makes factor IX, a blood clotting protein. At the same time they inserted a gene coding for integrase into some of the mice.

Within a week, mice that had received integrase injections had made 12 times more factor IX than those that had not, indicating that the integrase had inserted the factor IX gene through the binding of the attB site to the attP site in the mouse chromosome.

Furthermore, of the 53 possible integration sites, the factor IX gene was found to have inserted in only two places – with one being by far the more common location.

Calos now hopes to start human trials of the technique in a fatal childhood skin disease called recessive dystrophic epidermolysis bullosa (EB). “We have already tried this with mice and the system worked beautifully” she says.

Journal reference: Nature Biotechnology (DOI: 10.1038/nbt753)