K. Tsai et al., Age-related changes in the mitochondrial depolarization induced by oxidative injury in human peripheral blood leukocytes, FREE RAD RE, 35(4), 2001, pp. 395-403
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.