Fig. 3. How can mutation accumulation affect functional output of gene regulatory networks?

Cellular and organismal function is organized in complex gene regulatory networks (GRNs) involving interactions between large numbers of gene and their regulators, typically genes and their cis- and trans-acting elements. (A) Mutations inevitably accumulate in elements of each functional network in a stochastic manner. While initially insufficient in number to have an effect, eventually these mutations will collectively diminish the functional output of the GRN in an increasingly large number of cells, possibly through increased transcriptional noise (see text). (B) Increased noise in GRNs could explain defects in kinetics of cell signaling during aging, in which the response to external stimuli is blunted.