I'll freely admit to being very interested in research on aging and lifespan. It's a great subject from a scientific (and philosophical) point of view, but perhaps the prospect of turning 50 years old next year has something to do with it, too (not that that age seems anywhere near believable from my end).
Model organisms such as nematodes and fruit flies have already helped identify a number of highly conserved pathways that affect lifespan, many of them having to do with nutrient sensing and various insulin-related pathways. But there are other possibilities. One hallmark of aging at the cellular level is an accumulation of protein defects, chiefly misfolded and chemically modified proteins that apparently are difficult to clear out.
A new paper in Nature takes an alarmingly direct route to investigating potential therapies for this pathway. The researchers looked at small molecules that are known to bind tightly to insoluble protein aggregates and fibrils like amyloid. And what sort of compounds are we sure bind tightly to such things? Why, the sorts of dyes used to selectively stain them for histopathology slides, what else? (See, I told you that this was a rather forceful approach).
But it certainly seems to have paid off. As it turns out, treating nematodes (roundworms, C. elegans) with the dye Thioflavin T (also known as ThT or Basic Yellow 1) extends their lives quite significantly - up around a 60% increase in both median and maximal lifespan. Several other related benzazole compounds were also tried, which produced lifespan extension of up to 40%, and at much lower concentrations.
There are some nematode strains with known defects in protein handling - they produce extra amyloid or polyglutamine proteins, which eventually paralyze them and kill them off. Treating these with the dye had a significant lowering effect on the number of paralyzed nematodes, and the protein aggregrates in their muscle tissue were much lower as well. Similar effects were seen in several other mutant strains that had been used as markers of protein homeostasis.
A number of RNAi and immunological experiments (this is a very data-rich paper, by the way) indicated that ThT's effects depend on several known protein regulators and chaperones. In particular, a strain with a defective heat-shock factor 1 (HSF-1) gene showed no effects with ThT treatment at all, and neither do nematodes with an RNA knockdown of SKN-1 (also known to be implicated in stress responses and longevity). Taken together, these folks really do seem to have found a way to enhance the protein homeostasis functions of living cells, and this seems to have a very beneficial effect on their aging process.
Very interesting work, and very thoroughly followed up on, as it should be. I would be absolutely certain that similar experiments are underway in other species as we speak - I'd go straight to mice, personally, and not neglect some of the mutantmouse strains with protein-handling defects of their own, and compare them to mice that overexpress or underexpress HSF-1 itself. (I can't find any references to SKN-1 mutant mice). Those would be excellent experiments, but I'll bet that I'm not the only one who thinks so. In fact, I'll clean my lab bench off with my tongue if the people who did these studies haven't already thought of them, too.
Oh, and just one more thing: as my wife pointed out to me when I told her about this paper, the FDA was just making headlines the other day by recommending that more study be given to any possible links between food dyes and hyperactivity (though stopping short of recommending any warning at this time, due to lack of convincing evidence). On the basis of this latest work, though, I'm starting to wonder if we're not putting enough dyes in our food. . .