Theorizing on Gene Network Stability and Aging
Researchers here model the relationship between genetic regulation and aging with an eye towards trying to fit the outcomes in both negligibly senescent and "normally aging" species. It is known that advancing age brings with it epigenetic dysregulation, meaning significant changes in the levels of various proteins produced from their genetic blueprints, and therefore significant changes in cell behavior. Researchers differ on what this means and how close it is to the root causes of aging. In the theories in which aging is an accumulation of damage, then epigenetic changes are far downstream in the chain of cause and consequence; they are a reaction to rising levels of cell and tissue damage.
Several animal species are considered to exhibit what is called negligible senescence, i.e. they do not show signs of functional decline or any increase of mortality with age. Recent studies in naked mole rat and long-lived sea urchins showed that these species do not alter their gene-expression profiles with age as much as other organisms do. This is consistent with exceptional endurance of naked mole rat tissues to various genotoxic stresses. We conjectured, therefore, that the lifelong transcriptional stability of an organism may be a key determinant of longevity.We analyzed the stability of a simple genetic-network model and found that under most common circumstances, such a gene network is inherently unstable. Over a time it undergoes an exponential accumulation of gene-regulation deviations leading to death. However, should the repair systems be sufficiently effective, the gene network can stabilize so that gene damage remains constrained along with mortality of the organism. We investigate the relationship between stress-resistance and aging and suggest that the unstable regime may provide a mathematical basis for the Gompertz "law" of aging in many species. At the same time, this model accounts for the apparently age-independent mortality observed in some exceptionally long-lived animals.