Mitochondrial dysfunction has long been considered a key mechanism in the ageing process but surprisingly little attention has been paid to the impact of mitochondrial number or density within cells. Recent reports suggest a positive association between mitochondrial density, energy homeostasis and longevity. However, mitochondrial number also determines the number of sites generating reactive oxygen species (ROS) and we suggest that the links between mitochondrial density and ageing are more complex, potentially acting in both directions. The idea that increased density, (...) especially when combined with mitochondrial dysfunction, might accelerate ageing is supported by a negative correlation between mitochondrial density and maximum longevity in an interspecies comparison in mammals, and by evidence for an intimate interconnection between cellular ROS levels, mitochondrial density and cellular ageing. Recent data suggest that retrograde response, which activates mitochondrial biogenesis, accompanies cellular ageing processes. We hypothesise that increased mitochondrial biogenesis, and possibly also impaired degradation and segregation of mitochondria, if occurring as adaptation to pre‐existing mitochondrial dysfunction, might aggravate ROS production and thus actively contribute to ageing. BioEssays 29:908–917, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

An incoherent feed‐forward loop (FFL) is one of the most‐frequently observed motifs in biomolecular regulatory networks. It has been thought that the incoherent FFL is designed simply to induce a transient response shaped by a ‘fast activation and delayed inhibition’. We find that the dynamics of various incoherent FFLs can be further classified into two types: time‐dependent biphasic responses and dose‐dependent biphasic responses. Why do the structurally identical incoherent FFLs play such different dynamical roles? Through computational studies, we show that (...) the dynamics of the two types of incoherent FFLs are mutually exclusive. Following from further computational results and experimental observations, we hypothesize that incoherent FFLs have been optimally designed to achieve distinct biological function arising from different cellular contexts. Additional Supporting Information may be found in the online version of the article. BioEssays 30:1204–1211, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Several protective cellular mechanisms protect against the accumulation of reactive oxygen species (ROS) and the concomitant oxidative stress. Therefore, any reduction in glucose or fatty acid flux into cells leading to a decrease in the production of reducing equivalents would also lead to a decreased ROS production and protect cells against oxidative stress. In the presence of insulin, FOXO proteins are localized from the nucleus to the cytoplasm and degraded. An increase in cellular glucose uptake will lead to increased production (...) of ROS. This in turn activates the stress‐responsive Jun‐N‐terminal kinase (JNK), which promotes nuclear translocation of FOXO proteins, upregulating some important target genes including stress resistance. Consequently, insulin resistance should result in decreased cellular ROS production. For this reason, insulin resistance could be a physiological mechanism activated at the cellular level in response to conditions stimulating ROS production and leading to the prevention of oxidative stress, and extension of life. Concerning the whole organism, however, IR is a maladaptive process in the long term causing a diabetic state. BioEssays 29:811–818, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

The sociobiology of bacteria, largely unappreciated and ignored by the microbiology research community two decades ago is now a major research area, catalyzed to a significant degree by studies of communication and cooperative behavior among the myxobacteria and in quorum sensing (QS) and biofilm formation by pseudomonads and other microbes. Recently, the topic of multicellular cooperative behaviors among bacteria has been increasingly considered in the context of evolutionary biology. Here we discuss the significance of two recent studies1,2 of the phenomenon (...) of “cheating” mutants and their exploitation of cooperating microbial populations of Pseudomonas aeruginosa. BioEssays 30:296–298, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

The 'Evolution of Cooperation' addresses a simple yet age-old question; If living things evolve through competition, how can cooperation ever emerge? Despite the abundant evidence of cooperation all around us, there existed no purely naturalistic answer to this question until 1979, when Robert Axelrod famously ran a computer tournament featuring a standard game-theory exercise called The Prisoner's Dilemma. To everyone's surprise, the program that won the tournament, named Tit for Tat, was not only the simplest but the most "cooperative" entrant. (...) This unexpected victory proved that cooperation - one might even say altruism - is mathematically possible and therefore needs no hidden hand or divine agent to create and sustain it. A great roadblock to the understanding of all sorts of behavior was at last removed. The updated edition includes an extensive new chapter on cooperation in cancer cells and among terrorist organizations. (shrink)