Tuesday, August 10, 2010

Just Accepted. Hydrogen peroxide breathes life..!

New interesting paper in PNAS (Impact Factor 9.4)

Did you read the title carefully..?
I bet “Not”! So read it again.

How come catalase deletion, high levels of H2O2 lead to increased life span?
For years we have been told that free radicals damage our cells and leads to ageing.
But some recent studies have established at least in some organisms that Oxidative stress is indeed a positive regulator of extended lifespan.
In this paper, authors establish that elevated levels of hydrogen peroxide (either by catalase inactivation or Caloric Restriction) lead to increased lifespan of yeast. These findings are clearly in contrast with the long held theory claiming oxidative stress leads to ageing.
Interesting finding for peroxisome researchers in this paper, is that inactivation of peroxisomal catalase Cta1p results in extended life span which is further extended by caloric restriction.!
H2O2 levels increase as a result of CR or CAT1 deletion. It is assumed that the ROS will damage the cell and the cells should die early. But Authors found that increased lifespan due to increased hydrogen peroxide is by Hormesis effect. Elevated levels of H2O2 induce SOD activity and in turn reduce the levels of superoxide anion. H2O2 is now also established to be secondary messenger for diverse pathways.

Afterthoughts - extension of yeast Chronological lifespan by induction of H2O2 and SOD seems good at cellular level. But how can we be sure about the health of these cells during this extended lifespan. in case of humans, what we seek is extended lifespan but not the one filled with sick health and disabilities.!

Another peroxisome connection -
New Paper in journal "AGING"
Chemical genetic screen identifies lithocholic acid as an anti-aging compound that extends yeast chronological life span in a TOR-independent manner, by modulating housekeeping longevity assurance processes
Goldberg AA et al.
From the group of Prof.Vladimir Titorenko
The authors observed that pex5Δ mutation leads to shortening of chronological life span (CLS) in Calory Restricted (CR) yeast. (See Figure 1)
The authors used High-throughput chemical genetic screen which led to identification of Lithocholic acid (LCA) as a compound which extends CLS in pex5Δ cells under caloric restriction. The study was further extended to Wild type cells.

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