Linking proteostasis, aging, and brain ischemia

Cardiac arrest and ischemic stroke can lead to severe brain dysfunction, due to metabolic stress and loss of protein homeostasis (proteostasis). Further, both metabolic resilience and proteostasis deteriorate with aging, which renders cells inefficient in coping with pathologic consequences of brain ischemia. We describe how aging affects both intrinsic metabolic processes and proteostasis, including several branches of processing by which cells maintain a functional proteome. These pathways of proteostasis include the unfolded protein response, ubiquitination, SUMOylation, and autophagy. Our review further discusses the clinical relevance and how these elements can be pathologically modulated with cardiac arrest and ischemic stroke, as well as potential treatment strategies that may improve resilience and outcome with aging.