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October 26, 2010
Dapsone Prolongs Life? Well, In Nematodes It Does. . .
Get ready for the life-extension folks to jump on this one: there's a report out in PNAS that the longtime treatment for leprosy (Hansen's disease), diaminodiphenylsulfone (DDS or dapsone), also prolongs life in the nematode C. elegans.
We seem to be talking about nematodes a lot around here recently. The authors of the current study (from Korea) got around the dosing problem by feeding DDS to bacteria, and them feeding those to the nematodes. (When you can get away with that, it seems like the most reliable way of getting drugs into the little beasts). The nematodes accumulated the compound up to about 5 mg/kilo body weight - although I have to say, a kilo of nematodes is a rather alarming thought. The treated animals showed a significantly longer lifespan, faster body movements compared to untreated controls, and a delay in accumulating the "aging pigment" lipofuscin.
Now, DDS kills bacteria by inhibiting folate synthesis, but that doesn't seem to have anything to do with lifespan extension. The authors found that one of its key targets might be pyruvate kinase - and this might be the source for the mild anemia that's sometimes seen as a side effect in human patients. Nematodes have two isoforms of the enzyme, one mostly in muscle, and the other mostly in the digestive tract. Further study (with RNAi, etc.) showed that the lifespan extension seems to be working through the former, but not the latter. But it also showed that this probably can't be responsible for the whole lifespan effect, either: mutant nematodes with that isoform deleted live longer than wild type, but treating them with DDS makes them live longer still.
The authors point out that dapsone has been used in humans for a very long time, and that there's a 5% gel that's been shown to be safe for long-term treatment (and which reaches the blood levels that you'd think would be sufficient). They finish up by saying: "We suggest that is is worthwhile to examine whether DDS is effective in enhancing longevity in humans as well." There are enough people interested in these things that I think that this will be tried out very shortly, probably starting this week, albeit in a rather uncontrolled manner. . .
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