Age-related changes in the mitochondrial depolarization induced by oxidative injury in human peripheral blood leukocytes

Aging is associated with impaired immunity and reduced host defenses. Mitoc hondrial bioenergetic dysfunctions and reduced antioxidative ability of imm unocompetent cells may contribute to this phenomenon. In this study, 60 hea lthy volunteers of different age groups donated their blood after overnight fasting. Leukocytes were subjected to oxidative injuries by exposure to t- butylhydroperoxide, and were labeled with fluorochromes for measuring mitoc hondria transmembrane potential (Delta psi (m)), membrane peroxidation and mitochondrial oxidant formation. Delta psi (m) declined after t-butylhydrop eroxide exposure, and the change was more prominent in leukocytes from olde r individuals. Cyclosporin A partly restored Delta psi (m) implying the con tributing role of mitochondrial permeability transition pores. The mitochon drial. depolarization was accompanied by increased oxidant formation and ox idation of pyridine nucleotides, which were more prominent in older subject s. The results support the view that the bioenergetic functions of mitochon dria are more susceptible to oxidative injury in aged individuals. The decr eased ability of leukocytes to resist oxidative stress may contribute to im munosenescence in humans.