Abstract

Ageing is a process associated with tissue decline and the onset of numerous diseases. Once thought to be a random process driven by accumulated damage, we now know that ageing and the onset of age-associated disease can be influenced by both genetic and environmental factors. One characteristic of ageing is an accumulation of misfolded and aggregated proteins, which underlie many of the diseases associated with old age. These proteins accumulate as a result of an age-associated failure in the cellular stress responses that detect and clear damaged proteins. Focusing on the endoplasmic reticulum unfolded protein response (UPR), we are interested in how stress responses can be manipulated to increase health and longevity. In particular, we have found that activating the UPR in the nervous system of C. elegans activates a novel signaling pathway that leads to stress response activation in other tissues. We are now exploring the signaling mechanisms that allow this stress response activation to be communicated between tissues, and utilizing multiple approaches to understand how systemic stress response activation leads to increased health and longevity, with a view to harnessing this pathway for disease treatment.