Regular readers should by now know that accumulating damage to the mitochondria, the power plants of your cells, contributes to degenerative aging. That damage is a side-effect of being alive - it's something like corrosion in power plant internals, an by-product of operation. When I've talked about this in the past, it's usually in the context of the chain of consequences that occurs when free radicals (or reactive oxygen species) produced by the mitochondria damage mitochondrial DNA. Damage to the mitochondrial DNA eventually means that important proteins, part of the mitochondrial power-generating machinery, are no longer produced. It goes downhill from there.

Regular readers should also recall the evidence for glycation as a bad thing for your long term health. Sugars have a way of running rampant through your biochemistry, gumming together important molecules for a while in glycation reactions, and creating new biochemicals called advanced glycation endproducts (AGEs). The AGEs then trigger abnormal behavior in your cells via the receptor for AGE, or RAGE. The more gylcation that takes place, the more damage your metabolism suffers - and aging is all about rising levels of damage.

Last year, I mentioned a demonstration of life extension in nematode worms achieved by reducing the level of glycation. Researchers increased the levels of a natural enzyme called glyoxalase that reduces the levels of glycated chemicals: this is somewhat analogous to using antioxidants to reduce oxidative stress and levels of free radicals. Today, I noticed the following paper, which theorizes that glycation also causes damage to mitochondria, possibly by preventing vital mitochondrial proteins from doing their jobs, and that lower levels of glycation also reduce the problems that are characteristic of mitochondrial damage.

Dicarbonyls linked to damage in the powerhouse: glycation of mitochondrial proteins and oxidative stress

Protection of mitochondrial proteins from glycation by endogenous dicarbonyl compounds, methylglyoxal and glyoxal, was found recently to prevent increased formation of reactive oxygen species and oxidative and nitrosative damage to the proteome during aging and produce life extension in the nematode Caenorhabditis elegans.

This suggests that dicarbonyl glycation damage to the mitochondrial proteome may be a preceding event to mitochondrial dysfunction leading to oxidative stress. Future research will address the functional changes in mitochondrial proteins that are the targets for dicarbonyl glycation.

More direct evidence is needed to bolster this theory offered to explain the observed results - but isn't it interesting to see how everything links back to the mitochondria in one way or another?

Posted by Reason at September 18, 2008 7:13 PM | TrackBack (0)