Network theory explain aging dynamics

Dysregulation of gene expression patterns leads to the loss of cellular function during aging. The exact characteristics of the cellular loss of function depend on the specific up/down-regulated genes and vary between pathways and cell types. However, the mechanism behind this dysregulation remains elusive. Here we develop an analytical framework using network theory to characterize the impact of aging on the gene regulatory networks. We find that the accumulation of somatic mutations and changes in methylation levels result in a global loss of network stability. This leads to an increase in cellular susceptibility to changes which can explain cell-to-cell variability. We also find a slowdown in the response time to biochemical signals during aging. This could explain the inflammaging phenomena where the healthy process of inflammation does not shut down and turns chronic. It can also explain the slowing down in the healing process of wounds in old age. Our results highlight the importance of the complex gene regulation network in aging and provide an analytical framework bridging between the biology of aging and nonlinear dynamics.