The network concept is increasingly used for the description of complex systems. Here, we summarize key aspects of the evolvability and robustness of the hierarchical network set of macromolecules, cells, organisms and ecosystems. Listing the costs and benefits of cooperation as a necessary behaviour to build this network hierarchy, we outline the major hypothesis of the paper: the emergence of hierarchical complexity needs cooperation leading to the ageing (i.e. gradual deterioration) of the constituent networks. A stable environment develops cooperation leading (...) to over‐optimization, and forming an ‘always‐old’ network, which accumulates damage, and dies in an apoptosis‐like process. A rapidly changing environment develops competition forming a ‘forever‐young’ network, which may suffer an occasional over‐perturbation exhausting system resources, and causing death in a necrosis‐like process. Giving a number of examples we demonstrate how cooperation evokes the gradual accumulation of damage typical to ageing. Finally, we show how various forms of cooperation and consequent ageing emerge as key elements in all major steps of evolution from the formation of protocells to the establishment of the globalized, modern human society. (shrink)

Human life expectancy has increased dramatically through improvements in public health, housing, nutrition and general living standards. Lifespan is now limited chiefly by intrinsic senescence and its associated frailty and diseases. Understanding the biological basis of the ageing process is a major scientific challenge that will require integration of molecular, cellular, genetic and physiological approaches. This article reviews progress that has been made to date, particularly with regard to the genetic contribution to senescence and longevity, and assesses the scale of (...) the task that remains. (shrink)

The close link between signaling by the developmental regulators of the Hedgehog family and cholesterol biochemistry has been known for some time. The morphogen is covalently attached to cholesterol in a peculiar autocatalytic reaction and embryonal disruption of cholesterol synthesis leads to malformations that mimic Hh signaling defects. Recently, it was furthermore shown that secreted Hh could hitchhike on lipoprotein particles to establish its morphogenic gradient in the developing embryo. Additionally, there is new evidence that the Hh‐receptor Patched transmits the (...) Hh signal by modulating the secretion of an inhibitory sterol molecule from the receiving cells. Here we present some of the most recent discoveries on the Hh–sterol link and discuss their implications from a systems design perspective. We predict that a robust functioning of the Hh pathway will require the involvement of more sterol metabolites, and these should be the subject of future research. BioEssays 29:1085–1094, 2007. © 2007 Wiley Periodicals, Inc. (shrink)