Oxidative insult after ischemia/reperfusion in older adults

Abstract

Aging is associated with significant impairment in tolerance to acute stressors such as ischemia/reperfusion and this impairment appears to contribute to the increased morbidity and mortality of older adults compared to young adults in clinical conditions associated with ischemia/reperfusion. These conditions include ischemic heart disease, stroke, and a variety of surgeries. Ischemia leads to a transition from aerobic to anaerobic metabolism with subsequent depletion of ATP, accumulation of lactate, acidosis, and loss of intracellular ion homeostasis. Reperfusion results in increased oxidative stress and calcium overload which together stimulate pathways of necrosis and apoptosis. These adverse events are exaggerated in older individuals. In particular, oxidative stress plays a central role in the age-related increase in vulnerability to ischemia/reperfusion. We outline a useful forearm ischemia/reperfusion method to assess this vulnerability in older adults and have shown that several interventions can markedly improve resistance to ischemia/reperfusion.