Considering Rate-Limiting Processes in the Progression of Aging

In this paper, the author argues for greater emphasis to be placed on identifying rate-limiting processes in aging, here termed "flux-controlling" processes. One can tinker with various aspects of cellular metabolism connected to any one given molecule or class of molecules, and do so in many different ways, but any given approach may or may not interact with a rate-limiting step. If it doesn't, then the outcome will not tell us all that much about whether or not this molecule, this process, is important in aging. Let us imagine that Gustav Embden (1874-1933), one of the ingenious discoverers of glycolysis, would have had modern transgenic techniques at hand and intended to use them to investigate the role of phosphoglycerate kinase (PGK) in the biochemical degradation of glucose to pyruvate. He would have probably overexpressed the enzyme 10x first, and he would not have seen any relevant change in the rate of pyruvate formation in the perfused working heart, whereas the addition of insulin would have shown a clear effect. He then would have generated 90% knockdown animals and again would not have seen any decrease in the rate of glycolysis. Hence, he would have confidently concluded that PGK was not involved in glycolysis. Thus, he would have arrived at an overtly wrong conclusion (merely hypothetical; sorry, Gustav!). In essence, this is what we do today when we conclude from unsuccessful overexpression or knockdown studies of antioxidant enzymes that free ...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs