Amyloid-Binding Compound Extends Lifespan in C. Elegans
Gordon J. Lithgow, Ph.D.
The Buck Institute for Age Research
NIEHS Grant RL1ES016655
NIEHS supported-researchers at the Buck Institute for Age Research report that a chemical dye that lights up amyloid protein clumps characteristic of Alzheimer's disease also slows aging in the nematode, C. elegans. The lifespan-boosting effects of the dye - called Thioflavin T or Basic Yellow 1 - support the idea that the build-up of misshapen proteins is one of the fundamental events in the aging process. Drugs that stimulate the cell's natural repair and protein-recycling systems could be used to treat diseases of old age.
Misfolded proteins don't function properly and tend to accumulate and gum up other cellular systems. Worms genetically engineered to have a revved-up protein-recycling system, for instance, live longer than normal worms.
The study results show that small doses of Thioflavin T boosted the lifespan of roundworms by as much as 78%. Worms that did not receive the dye were all dead within 20 days, yet more than 80% of worms consuming a diet that included an optimum dose of Thioflavin T were still alive after the same period. Thioflavin T proved toxic at higher doses and shortened the worms' lives considerably.
The study authors suspect that Thioflavin T boosts lifespan by recognizing all kinds of toxic protein clumps. The dye reversed the effects of mutations that cause muscle proteins to misfold, and to become paralysed at a particular temperature. The team also found that worms that lack genes important to dealing with misshapen proteins do not live longer when fed Thioflavin T.
Citation: Alavez S, Vantipalli MC, Zucker DJ, Klang IM, Lithgow GJ. Amyloid-binding compounds maintain protein homeostasis during ageing and extend lifespan. Nature. 2011 Apr 14;472(7342):226-9.
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