I noticed a paper on the modulation of damaging reactive oxygen species generated by the mitochondria today - this should sound familiar to some of you. Mitochondria are the power plants of your cells, and like all power plants they generate waste as a consequence of their operation. That waste is an important root cause of aging; the rate at which it is produced and your resistance to its damaging effects are strong determinants of longevity.

Even though the researchers in this paper don't have life span data, they are putting together a system very similar to gene-engineered mice that overexpress catalase in their mitochondria. The antioxidant catalase soaks up some portion of the reactive oxygen species - also known as free radicals - before they can wreck havoc with cellular machinery, and the mice live longer as a result. A Russian researcher has crafted a similar demonstration in recent years using biochemistry instead of genetics to localize ingested antioxidants into the mitochondria - there also, longer-lived mice.

Here is the PubMed reference for the paper that caught my eye today:

H(2)O(2) [or hydrogen peroxide] is a major reactive oxygen species produced by mitochondria that is implicated to be important in aging and pathogenesis of diseases such as diabetes; however, the cellular and physiological roles of mitochondrial H(2)O(2) remain poorly understood.

Peroxiredoxin 3 (Prdx3/Prx3) is a thioredoxin peroxidase localized in mitochondria, [which means that this antioxidant chemical can neutralize some fraction of the H(2)O(2) at source, before those free radicals get out into the cell].

To understand the cellular and physiological roles of mitochondrial H(2)O(2) in aging and pathogenesis of age-associated diseases, we generated transgenic mice overexpressing Prdx3 (Tg(PRDX3) mice). Tg(PRDX3) mice overexpress Prdx3 in a broad range of tissues, and the Prdx3 expression is localized exclusively in the mitochondria.

As a result of increased Prdx3 expression, mitochondria from Tg(PRDX3) mice produce significantly reduced amount of H(2)O(2), and cells from Tg(PRDX3) mice have increased resistance to stress-induced cell death and apoptosis. Interestingly, Tg(PRDX3) mice show improved glucose homeostasis, as evidenced by their reduced levels of blood glucose and increased glucose clearance. Tg(PRDX3) mice are also protected against hyperglycemia and glucose intolerance induced by high-fat diet feeding.

I'll wager that these mice also live significantly longer, protected to some degree from the biochemical side-effects of a working metabolism by the enhanced levels of the antioxidant peroxiredoxin 3. That data is a good few years out, however, even if the researchers are working on it now.

I suppose this is a good time to remind folk that ingesting plain old antioxidants is of no demonstrated benefit - they aren't going anywhere near your mitochondria, which is the only place that much matters, so it seems:

Since the early 1990s scientists have been putting these compounds through their paces, using double-blind randomised controlled trials - the gold standard for medical intervention studies. Time and again, however, the supplements failed to pass the test. True, they knock the wind out of free radicals in a test tube. But once inside the human body, they seem strangely powerless. Not only are they bad at preventing oxidative damage, they can even make things worse. Many scientists are now concluding that, at best, they are a waste of time and money. At worst they could be harmful." Mouse studies have shown that carefully directing antioxidants to the cellular mitochondria extends healthy life span on the order of 20-30% - a fairly complex feat of biochemical engineering that no presently available pill can match. Those studies further showed no benefit from the same antioxidants sent elsewhere in mouse biochemistry. Haphazardly throwing chemicals at a very complex problem and hoping for the best does not have the best record of success - when that's all you can do, you do it, but we can do better now.

To recap: a demonstrated 20-30% extension of mouse life span through the very latest methods of engineering antioxidants into the mitochondria, presently available for purchase nowhere. On the flip side, there is zero benefit for mice resulting from the antioxidants presently sold in attractive little jars. Caveat emptor.

Posted by Reason at September 10, 2008 7:24 PM | TrackBack (0)