Dye used in Alzheimer’s research promotes longevity in lab nematodes
One secret to living a longer life — be a worm.
Wriggly roundworms (Caenorhabditis elegans), it seems, have found themselves a new philosopher’s stone. Doses of a dye used to visualize the proteins that build up in the brains of Alzheimer’s patients can up worm life span by more than half, California researchers report online March 30 in Nature. The dye, called thioflavin T, seems to prevent the deviant protein clumps often associated with a number of human age-related diseases, including Alzheimer’s, researchers say.
During aging, the body accumulates proteins that aren’t shaped, or “folded,” the way they should be, says Richard Morimoto, a molecular biologist at Northwestern University in Evanston Ill. Like replacing finely tuned engine components with parts from a 30-year-old Yugo, those proteins don’t work and can even damage entire organs. “All of a sudden, your Porsche isn’t running like a Porsche,” Morimoto says.
Misshapen proteins, for reasons that remain a hot topic of study, often sit in big clumps called aggregates. Such clumps have been spotted in any number of chronic illnesses from Alzheimer’s to Parkinson’s and Huntington’s disease. “The underpinning for all these diseases may be aging,” Morimoto says. Longer, healthier life may be possible, then, if doctors can keep misshapen proteins under wraps.
That makes thioflavin T a potential protein mechanic. The California team fed the dye to roundworms genetically prone to getting debilitating clumps of protein in their muscles — the same kind of protein present in the brains of Alzheimer’s sufferers. Thioflavin T blocked many of those clumps from accumulating in the treated worms. Normal worms lived longer after eating the chemical, too. Simply put, “proteins that are likely to become unfolded don’t,” says study coauthor Gordon Lithgow, a molecular geneticist at the Buck Institute for Research on Aging in Novato, Calif.
What’s going on in the worms isn’t clear yet. The dye seems to bind directly to misshapen proteins, which is why researchers use it to look at Alzheimer’s clumps under the microscope, and may change the shape of those proteins.
But the dye doesn’t work alone. Some of the critters’ normal stress responses are necessary to block clumping, too. These responses, very similar to those in other animals like humans, help to shape proteins as cells churn them out and may even churn out antioxidants that protect proteins from damage. Lithgow suspects that the dye begins the process, fudging the shapes of bad proteins. That then tips the body off to the problem, and the normal stress responses come in and “take out the garbage,” he says.
There’s a lot of medical potential here, Lithgow adds: “This area of protein aggregation should be thought about for developing treatments for age-related diseases.”
Going from worm to mammal is not easy, says Chris Link, a molecular geneticist at the University of Colorado at Boulder. Drugs that work in muscles may not be able to cross into the brain at all. “Whether they would actually work for neurologic diseases isn’t clear because they may not get to where they need to be,” he says.
But healthy people may have another way to trigger the same stress responses as thioflavin T. In an earlier study, Link and his colleagues showed that certain chemicals in coffee also seemed to slow the formation of protein clumps, potentially by triggering wormy antioxidants.
Now, coffee: That’s one delicious fountain of youth.
R.I. Morimoto. Proteotoxic stress and inducible chaperone networks in neurodegenerative disease and aging. Genes & Development, Vol. 22, June 1, 2008, p. 1427-1438. [Go to]
S. Alavex et al. Amyloid-binding compounds maintain protein homeostasis during ageing and extend life span. Nature. doi: 10.1038/nature09873.