Perturbation of bulk and selective macroautophagy, abnormal UPR activation and their interplay pave the way to immune dysfunction, cancerogenesis and neurodegeneration in ageing

A plethora of studies has indicated that ageing is characterized by an altered proteostasis, ROS accumulation and a status of mild/chronic inflammation, in which macroautophagy reduction and abnormal UPR activation play a pivotal role. The dysregulation of these inter-connected processes favors immune dysfunction and predisposes to a variety of several apparently unrelated pathological conditions including cancer and neurodegeneration. Given the progressive ageing of the population, a better understanding of the mechanisms regulating autophagy, UPR and their interplay is needed in order to design new therapeutic strategies able to counteract the effects of ageing and concomitantly restrain the onset/progression of age-related diseases that represent a private and public health problem.