Catalase-Based Longevity Not Replicated In Mice

Never a straight road in the life sciences. The extension of mouse life span by genetic modification to target the antioxidant catalase to the mitochondria is a result I've considered important for years, but another study finds no benefit to life span: "We evaluated the effect of overexpressing antioxidant enzymes on the lifespans of transgenic mice that overexpress CuZnSOD, catalase, or combinations of either CuZnSOD and catalase or CuZnSOD and MnSOD. Our results show that the overexpression of these major antioxidant enzymes, which are known to scavenge superoxide and hydrogen peroxide in the cytosolic and mitochondrial compartments, is insufficient to extend lifespan in mice." So something more complex is going on here; back to square one, and more studies to try and understand how it is that earlier results of extended healthy life were in fact produced.



I've just seen this today as a result of your (Reason's) linking to it in today's post. Note that this study does not in any way contradict the previous finding of life extension with catalase: in the previous study, as you note, catalase was ectopically targeted to the mitochondria, where the cell's main source of free radical production is inconveniently adjacent to the mitochondrial DNA, thus driving mtDNA damage and in particular mitochondrial DNA deletions, which are a driver of degenerative aging. In this location, being able to detoxify hydrogen peroxide prevented mtDNA deletions and extended lifespan.

In the study referenced here, they were just overexpressing normal catalase, which is localized in the peroxisomes: thus, it had no opportunity to interdict mtROS before damaging the mtDNA. One would expect little or no benefit from this, and indeed they got none.

Posted by: Michael at October 20th, 2016 1:42 PM

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