Dye extends life (if you're a worm)

“Scientists have discovered a dye that could slow down the ageing process in humans,” the Daily Express has reported. According to the newspaper, the yellow dye is a compound that is currently used in neuroscience laboratories to detect damaged proteins seen in the brains of patients with Alzheimer’s disease.

The laboratory study behind this report found that worms lived up to 70% longer when they were exposed to Thioflavin T (ThT), a dye commonly used in the laboratory to stain protein in cells. The dye also reversed the paralysis caused by their muscle cells accumulating amyloid proteins, which are implicated in Alzheimer’s disease.

While the findings will be of interest to scientists, these are preliminary results and the effects of this dye on human health are unclear. Potential new treatments for humans face a long timeline of testing and review to determine whether they are safe and effective. It is unlikely the systems in the worms are comparable with what might happen in the human body, and it remains to be seen whether ThT can be used to extend life.

Where did the story come from?

The study was carried out by researchers from the Buck Institute for Research on Aging, the Dominican University in California and the Karolinska Institute in Sweden. The work was supported by the Larry L Hillblom Foundation and the US National Institutes of Health. Individual researchers also received support from various organisations. The study was published in the peer-reviewed scientific journal Nature.

Newspaper headlines have generally featured claims that the key to longevity has been discovered, which detracts from the reality that this was a study in worms. Also, this was early research and it is likely that a lot of further research will be needed before we can tell if this technology is applicable to humans.

What kind of research was this?

The researchers say that studies have shown that the maintenance of a careful balance of protein in cells is linked to cell longevity. They hypothesise that providing animals with treatments that promote this balance may improve lifespan. They tested this theory in a laboratory experiment using adult worms known as Caenorhabditis elegans. These small worms usually live in the soil but are commonly studied in laboratory settings. The particular substance studied is Thioflavin T (ThT). This is dye often used in a laboratory setting to stain cells that are examined under a microscope. It specifically marks the presence of fibrous protein complexes, such as the amyloid proteins implicated in Alzheimer’s disease.

What did the research involve?

The researchers tested a number of substances for their effects on the balance of proteins in worms. The substances were:

• Thioflavin T (ThT)
• Curcumin (turmeric)
• 2-(2-hydroxyphenyl)-benzoxazole (HBX)
• 2-(2-hydroxyphenyl) benzothiazole(HBT)
• 2-(2-aminophenyl)-1H-benzimidazole (BM)
• Rifampicin (an antibiotic)

The worms were exposed to the different substances and to different doses of them by saturating the medium in the dishes the worms were growing in. Every second day the researchers assessed whether the worms on the plate were alive, dead or lost. They rated worms that did not respond to touch as dead.

In other experiments, they used worms that had been genetically modified to have diseases in which proteins accumulated in muscle tissue. These proteins were amyloid beta and polyglutamine (polyQ) protein. Amyloid beta is also associated with lesions in Alzheimer’s disease.

Worms unable to regulate this protein develop lesions in their muscles and become paralysed. The researchers exposed these diseased worms to the ThT and to the other compounds to determine whether they were able to restore protein regulation in the worms. They also undertook a series of other experiments designed to help them understand what processes ThT was acting upon in order to affect lifespan.

What were the basic results?

Exposure to ThT throughout life increased the average lifespan of the worms by about 60% and by 43-78% beyond their untreated maximum lifespan. However, at high doses, ThT was toxic and reduced lifespan. At all ages, treatment with ThT resulted in reductions in rates of age-specific mortality and in age-related decline in spontaneous movement. This indicated improved health.

Treatment with ThT was able to restore movement in those worms that were paralysed by lesions of amyloid beta (the protein found in brains with Alzheimer’s disease).

The effects of ThT on lifespan depended on the presence of other molecules (skn-1 transcription factor and a regulator molecular called HSF-1). The researchers say that ThT mimics the stress response that ultimately leads to better regulation of protein, stopping them from aggregating (i.e. collecting together to form clumps).

How did the researchers interpret the results?

The researchers conclude that their study has shown that molecules which can mimic the stress response and target the complex processes that regulate the balance of proteins in cells may "provide opportunities for intervention in ageing and age-related disease".

Conclusion

This well-described laboratory study has found that a dye commonly used in the laboratory to help identify the presence of protein complexes in cells actually interacts with these proteins in a beneficial way that could prevent them building up in cells. This effect appears to increase the lifespan of nematode worms and to reduce (or reverse) the age-related paralysis that occurs when amyloid lesions build up in their muscle cells.

As amyloid beta lesions are responsible for Alzheimer’s disease in humans, many newspapers have made the leap from these discoveries to a potential ability to extend human longevity using the Thioflavin T (ThT) dye studied. It is too soon to know whether ThT could be safely given to humans and whether it will have any effect on the lifespan of individuals.

News headlines that have suggested that ThT is the key to long life are overly optimistic given the early stage of this research. For example, the Daily Mail reported that ThT ‘slowed the symptoms of dementia in worms bred to mimic aspects of Alzheimer’s’. It is not clear where this claim has come from or indeed, what the symptoms of dementia might be in a worm.