Worms and Stress: Live Long and Prosper

This is a very interesting paper about worms. The central thing to remember is that it is about WORMS. Most of us are not worms, but all of us do have mitochondria. Worm mitochondria are, I suspect, quite similar to human mitochondria, at least as far as basic signaling mechanisms are concerned.

Glucose, as a molecule, is full of oxygen. One oxygen atom per pair of hydrogen atoms. You just need to add an oxygen molecule for each carbon atom to get just over 40 molecules of ATP. Fats are different. There are only two oxygen atoms down at one end of that long string of carbon and hydrogen. To extract the stored energy requires much more molecular oxygen, so makes more use of mitochondrial respiration.

The electron transfer chain leaks free radicals. Running your metabolism on fat requires more use of the electron transfer chain. That means more free radicals.

Generally free radicals are considered to be a Bad Thing.

Actually, if you think about it, having your white blood cells throw free radicals at invading bacteria suggests that free radicals are one reason we are all still alive. Nothing is all bad.

So worms, under glucose restriction, generate far more free radicals than those able to access glucose.

Here's the best bit: The ones making all the free radicals also live longer. Don't forget, it's only a worm!

Why do they live longer? Because mitochondria can only work by using oxygen to run the respiratory chain. If using mitochondrial respiration was damaging, we wouldn't do it! It's POTENTIALLY damaging. Given the few billion years we've had, metabolism would have stopped this free radical production if it needed to. Evolution hasn't made the respiratory chain leak proof. Why? Free radical generation is the signal that mitochondrial respiration is happening and it's time to up regulate the cell's routine protection against free radical damage that has stood the test of time. This does not involve going off and eating some poor plant to steal its antioxidants.

Catalase, superoxide dismutase and glutathione peroxidase will do for a start. These are local antioxidant enzymes produced where they are needed, when they are needed by a cell which needs them to run its power plants safely. The fact that they seem to have overall benefits, apart from the smooth running of the mitochondria, is a useful spin off. And they don't involve eating anything green.

There are a few summary points to the study:

Glucose restriction by any technique extends lifespan in worms.

Glucose supplementation produces a dose related shortening of life span in worms.

Glucose supplemented worms store FAT!

N-acetylcysteine, ascorbate or a vitamin E derivative (Trolox) each eliminates the life extension provided by glucose restriction in worms.

Here's the consolation for people knocking back the antioxidants: They probably do no harm directly, just eliminates any benefit from glucose restriction. If you live on glucose, well shrug...

This is how this research group view the impact of their work on diabetes management:

"In light of our findings, the current body of evidence tentatively calls into question the efficacy of increasing cellular glucose uptake in diabetics and suggests that other methods of lowering blood glucose (Isaji, 2007; Wright et al., 2007) may be preferable to achieve normal life expectancy in human type 2 diabetes patients."

The two refs cited refer to techniques for extracting glucose through the kidneys or possibly reducing its uptake through the gut. No consideration seems to be given to not actually putting quite so much glucose in to the system in the first place!


If anyone finds this remotely interesting, while not feeling particularly worm-like, you can go and look at the evidence in Jenny Ruhl's post on antioxidants in humans.

I'd just like to point you towards this particular one. I was surprised that as little as 1000mg of ascorbate per day with 400iu of vitamin E had a measurable effect. But, if the study is replicable, it might well fit in with the observational evidence.

Really must give up the chocolate (only kidding, my liver will save me!).

Peter