Although it has long been suggested that accumulation of errors in transcription and translation is one of the most important molecular mechanisms leading to ageing , a quantitative link between the error accumulation dynamics and mortality of species has so far remained elusive. We study stability properties of a generic gene regulatory network (GRN) and demonstrate that phenomenology of ageing and the associated population mortality rate can be naturally described in terms of critical dynamics of gene regulation and metabolic profiles. We analyze age-dependent microarray datasets and metabolic profiles forDrosophila melanogaster and explicitly show that the resulting GRNs are nearly critical and inherently unstable. This instability manifests itself as ageing in the form of exponential distortions of gene expressions and metabolic profiles with age, and causes the characteristic increase in mortality rate with age as described by  the Gompertz law. On top of that we explain the plateau in mortality rates observed at very late ages for large populations. We show that ageing contains both a stochastic component, related to regulatory error accumulation in transcription/translation/metabolic pathways , and a strong deterministic component, which can be naturally associated with a part of a development programme. We conclude on this basis that two opposing hypotheses of ageing, error accumulation and programmed ageing are in fact compatible with each other. Since mortality in humans, where it is characterized best, is mostly associated with age related diseases, we support the idea of ageing being the driving force behind the development of major diseases.
Although accumulation of molecular damage is suggested to be an important molecular mechanism of aging , a quantitative link between the dynamics of damage accumulation and mortality of species has so far remained elusive. To address this question, we examine stability properties of a generic gene regulatory network (GRN) and demonstrate that many characteristics of aging and the associated population mortality rate emerge as inherent properties of the critical dynamics of gene regulation and metabolic levels. Based on the analysis of age-dependent changes in gene-expression and metabolic profiles in Drosophila melanogaster, we explicitly show that the underlying GRNs are nearly critical and inherently unstable. This instability manifests itself as aging in the form of distortion of gene expression and metabolic profiles with age, and causes the characteristic increase in mortality rate with age as described by a form of the Gompertz law. In addition, we explain late-life mortality deceleration observed at very late ages for large populations. We show that aging contains a stochastic component, related to accumulation of regulatory errors in transcription/translation/metabolic pathways due to imperfection of signaling cascades in the network and of responses to environmental factors. We also establish that there is a strong deterministic component, suggesting genetic control. Since mortality in humans, where it is characterized best, is strongly associated with the incidence of age-related diseases, our findings support the idea that aging is the driving force behind the development of chronic human diseases.
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