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. Mitochondrial bioenergetic dysfunctions and reduced antioxidative ability of immunocompetent cells may contribute to this phenomenon. In this study, 60 healthy 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 mitochondria transmembrane potential (delta psi m), membrane peroxidation and mitochondrial oxidant formation. delta psi m declined after t-butylhydroperoxide exposure, and the change was more prominent in leukocytes from older individuals. Cyclosporin A partly restored delta psi m, implying the contributing role of mitochondrial permeability transition pores. The mitochondrial depolarization was accompanied by increased oxidant formation and oxidation of pyridine nucleotides, which were more prominent in older subjects. The results support the view that the bioenergetic functions of mitochondria are more susceptible to oxidative injury in aged individuals. The decreased ability of leukocytes to resist oxidative stress may contribute to immunosenescence in humans.
Tsai
K
K
Oxidative Stress Clinical Research Group, Section of Critical Care, Department of Medicine, Veterans General Hospital, National Yang-Ming University School of Medicine, Taipei, Taiwan. kctsai@vghtpe.gov.tw
Hsu
T G
TG
Lu
F J
FJ
Hsu
C F
CF
Liu
T Y
TY
Kong
C W
CW
D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D002460:Cell Line; D016572:Cyclosporine / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008875:Middle Aged; D008928:Mitochondria / Q000502:physiology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020122:tert-Butylhydroperoxide