Stress induced telomere shortening: longer life with less mutations?

BACKGROUND: Mutations accumulate as a result of DNA damage and imperfect DNA repair machinery. In higher eukaryotes the accumulation and spread of mutations is limited in two primary ways: through p53-mediated programmed cell death and cellular senescence mediated by telomeres. Telomeres shorten at every cell division and cell stops dividing once the shortest telomere reaches a critical length. It has been shown that the rate of telomere attrition is accelerated when cells are exposed to DNA damaging agents. However the implications of this mechanism are not fully understood. RESULTS: With the help of in silico model we investigate the effect of genotoxic stress on telomere attrition and apoptosis in a population of non-identical replicating cells. When comparing the populations of cells with constant vs. stress-induced rate of telomere shortening we find that stress induced telomere shortening (SITS) increases longevity while reducing mutation rate. Interestingly, however, the effect takes place only when genotoxic stresses (e.g. reactive oxygen species due to metabolic activity) are distributed non-equally among cells. CONCLUSIONS: Our results for the first time show how non-equal distribution of metabolic load (and associated genotoxic stresses) combined with stress induced telomere shortening can delay aging and minimize mutations

Degree Landscapes in Scale-Free Networks

We generalize the degree-organizational view of real-world networks with broad degree-distributions in a landscape analogue with mountains (high-degree nodes) and valleys (low-degree nodes). For example, correlated degrees between adjacent nodes corresponds to smooth landscapes (social networks), hierarchical networks to one-mountain landscapes (the Internet), and degree-disassortative networks without hierarchical features to rough landscapes with several mountains. We also generate ridge landscapes to model networks organized under constraints imposed by the space the networks are embedded in, associated to spatial or, in molecular networks, to functional localization. To quantify the topology, we here measure the widths of the mountains and the separation between different mountains.Comment: 4 pages, 5 figure

Ecosystems with mutually exclusive interactions self-organize to a state of high diversity

Ecological systems comprise an astonishing diversity of species that cooperate or compete with each other forming complex mutual dependencies. The minimum requirements to maintain a large species diversity on long time scales are in general unknown. Using lichen communities as an example, we propose a model for the evolution of mutually excluding organisms that compete for space. We suggest that chain-like or cyclic invasions involving three or more species open for creation of spatially separated sub-populations that subsequently can lead to increased diversity. In contrast to its non-spatial counterpart, our model predicts robust co-existence of a large number of species, in accordance with observations on lichen growth. It is demonstrated that large species diversity can be obtained on evolutionary timescales, provided that interactions between species have spatial constraints. In particular, a phase transition to a sustainable state of high diversity is identified.Comment: 4 pages, 4 figure

Hierarchy Measures in Complex Networks

Using each node's degree as a proxy for its importance, the topological hierarchy of a complex network is introduced and quantified. We propose a simple dynamical process used to construct networks which are either maximally or minimally hierarchical. Comparison with these extremal cases as well as with random scale-free networks allows us to better understand hierarchical versus modular features in several real-life complex networks. For random scale-free topologies the extent of topological hierarchy is shown to smoothly decline with $\gamma$ -- the exponent of a degree distribution -- reaching its highest possible value for $\gamma \leq 2$ and quickly approaching zero for $\gamma>3$.Comment: 4 pages, 4 figure

Circuit architecture explains functional similarity of bacterial heat shock responses

Heat shock response is a stress response to temperature changes and a consecutive increase in amounts of unfolded proteins. To restore homeostasis, cells upregulate chaperones facilitating protein folding by means of transcription factors (TF). We here investigate two heat shock systems: one characteristic to gram negative bacteria, mediated by transcriptional activator sigma32 in E. coli, and another characteristic to gram positive bacteria, mediated by transcriptional repressor HrcA in L. lactis. We construct simple mathematical model of the two systems focusing on the negative feedbacks, where free chaperons suppress sigma32 activation in the former, while they activate HrcA repression in the latter. We demonstrate that both systems, in spite of the difference at the TF regulation level, are capable of showing very similar heat shock dynamics. We find that differences in regulation impose distinct constrains on chaperone-TF binding affinities: the binding constant of free sigma32 to chaperon DnaK, known to be in 100 nM range, set the lower limit of amount of free chaperon that the system can sense the change at the heat shock, while the binding affinity of HrcA to chaperon GroE set the upper limit and have to be rather large extending into the micromolar range.Comment: 17 pages, 5 figure