Maintenance of protein homeostasis in glia extends lifespan in C. elegans

Mounting evidence support that glia play a key role in organismal ageing. However, the mechanisms by which glia impact ageing are not understood. One of the processes that has significant impact on the rate of ageing is the unfolded protein response. The more robust the UPR, the more the organism can counteract the effect of environmental and genetic stressors. However, how decline of cellular UPR translates into organismal ageing and eventual death is not fully understood. Here we discuss recent findings highlighting that neuropeptides released by glia act long distance to regulate ageing in C. elegans. Taking advantage of the short lifespan and the genetic amenability of this organism, the endoplasmic reticulum unfolded protein responses (UPR^ER) can be activated in C. elegans glia. This leads to cell-nonautonomous activation of the UPR^ER in the intestine. Activation of intestinal UPR^ER requires the function of genes involved in neuropeptide processing and release, suggesting that neuropeptides signal from glia to the intestine to regulate ER stress response. Importantly, the cell-nonautonomous activation of UPR^ER leads to extension of lifespan. Taken together, these data suggest that environmental and genetic factors that impact the response of glia to stress have the potential to influence organismal ageing. Further research on the specific neuropeptides involved should cast new light on the mechanism of ageing and may suggest novel anti-ageing therapies.