A new approach to aging research: Death as a tipping point

Single-mutant screens in the nematode C. elegans have shown to be successful in identifying genes that increase a healthy lifespan in the model organism. However, in spite of the presence of most of these genes in humans, only very few could also be associated with human longevity. One of the underlying reasons is that aging is a multifactorial complex trait influenced by a network of interacting processes. Studying the genetic processes leading to senescence are further complicated by the higher complexity of the human genome. Therefore, it is essential 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 in complex dynamic systems – a concept taken from ecology – to study and discover gene networks closely linked to aging.
Tipping points of collapse in ecological systems are characterized by a sudden and catastrophic shift between two alternative stable states. Before the transition, these systems often appear stable on 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 collapse. The theory predicts that early warning signals precede the occurrence of a tipping point. 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 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.