Some aging research progress
There have been a couple of interesting ageing papers recently. One showing how caloric restriction works through a mechanism involving hydrogen peroxide and another on flushing out old cells in mice. Some people think I am little extreme in my views about the free radical theory of aging being dead, but I am right here. We do not just burn up or wear out and both of these studies shed light on how this works. We age because we cannot maintain the fine balance to perfectly control our repair and maintenance processes indefinitely. The beauty of the connection of hydrogen peroxide (H2O2) to caloric restriction is that H2O2 is also a signalling molecule that can affect phosphorylation pathways. This helps to connect all of the known aging metabolic pathways to the balance of highly reactive forms of oxygen that can act as monitors of metabolic activity and stress. The difference between this emerging theory and the old free radical theory is that it is the balance, and not the direct damage from these reactive and unstable signalling molecules that is important. Unfortunately, the authors and the reviewers are both still hung up on the old free radical theory and seem to be missing the point by describing the process in terms of H2O2 resistance. Caloric restriction increases the expression of an enzyme that re-activates a peroxiredoxin (an enzyme that changes H2O2 to water) reducing the amount of H2O2. The unasked question is why would lower glucose levels require a greater ability to scavenge free radicals? The whole system is tied into a feedback loop so H2O2 levels would seem to remain elevated in the presence of normal or excessive levels of glucose. I fear that this paper is just going to add yet more fuel to the dying fire of the old free radical theory.
The other paper is also very interesting from a systems biology point of view. What they essentially did was to improve the mechanisms for removing dying cells. They made a mouse with a “kill this cell now” gene controlled by a promoter linked to a gene that tells sick and dying cells to eventually die. In these genetically modified mice, one can trigger the ”kill this cell gene” with a drug so that sick and dying cells are more quickly removed. The result is an improvement in overall maintenance and less age related problems for the animal as a whole. Interestingly, this shows that dying cells are not necessarily important for signalling repair mechanisms or the animals would have been less healthy. The other good thing is that these authors noted that they only tested on one genetic background. Aging effects are notoriously dependent on all levels of environmental effects from the genetic to physiological and even social. The H2O2 study above was done with yeast which are strange in the way they age (not multicellular) and needs to be explored in much more detail in animals and across genetic backgrounds as well. So some progress, but no sign of immortality in our immediate futures.