  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, and do not have measurable reductions in reproductive
capacity with age. Recent studies in Naked Mole Rat (NMR) and long- lived sea
urchin showed that the level of gene expression changes with age is lower than
in other organisms. These phenotypic observations correlate well with
exceptional endurance of NMR tissues to various genotoxic stresses. Therefore,
the lifelong transcriptional stability of an organism may be a key determinant
of longevity. However, the exact relation between genetic network stability,
stress-resistance and aging has not been defined. We analyze the stability of a
simple genetic- network model of a living organism under the influence of
external and endogenous factors. We demonstrate that under most common
circumstances a gene network is inherently unstable and suffers from
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, which may then enjoy a remarkable degree of stability over very
long times. We clarify the relation between stress-resistance and aging and
suggest that stabilization of the genetic network may provide a mathematical
explanation of the Gompertz equation describing the relationship between age
and mortality in many species, and of the apparently negligible senescence
observed in exceptionally long-lived animals. The model may support a range of
applications, such as systematic searches for therapeutics to extend lifespan
and healthspan.
