Death as a tipping point-Merging disciplines to predict lifespan

Aging is a multifactorial, complex trait resulting from a vast network of interacting genetic and environmental processes. In model organisms, aging is often studied in a reductionist approach by enhancing or limiting the function of individual genes to identify key-players within the complex genetic network of aging. While this approach has been instrumental to identify some central genes within processes, such as the cellular stress response, only very few of these genes could also be associated with human longevity.
We propose to complement reductionist mutant analyses with more system-oriented approaches based on new paradigms. Considering the complex nature of aging, we propose to use the paradigm of catastrophic regime shifts of complex dynamic systems to study and discover gene networks closely linked to aging. This paradigm has been applied to study the collapse of complex systems in many disciplines ranging from ecology, economics to sociology. In spite of the diverse underlying nature of these complex systems, they have common characteristic traits. The systems often appear stable for a wide range of external conditions until a point is reached at which stability can no longer be maintained. At this point, slight changes in the environment lead to a sudden shift to a distinct alternative stable state. This point is known as the tipping point of collapse. We hypothesize that the aging process in C. elegans follows the characteristics of a complex system with death as the result of a tipping point. More importantly, the paradigm describes early warning signals that predict the occurrence of a system collapse. One of the indicators is the slowing down of the recovery rate from transient perturbations as the system approaches a tipping point. In C. elegans, a close link between the resistance to stress perturbations and lifespan has long been established. We will introduce the concept of using C. elegans stress response in combination with the paradigm of catastrophic regime shifts to study aging as a complex trait with the ultimate aim of predicting death.