Mitochondrial dysfunction in lymphocytes from old mice: enhanced activation of the permeability transition.
Aging is associated with mitochondrial dysfunction in excitable tissues such as nerve and muscle. However, it is not known if immunosenescence is similarly associated with mitochondrial dysfunction in lymphocytes. We have found that spleen lymphocytes from old mice have lower respiration rates than lymphocytes from young mice. Cyclosporin, an inhibitor of the mitochondrial Permeability Transition, PT, restored normal respiration rates to lymphocytes from old mice, suggesting enhanced susceptibility to PT activation. Lymphocytes from old mice also had a lower mitochondrial membrane potential (delta psi m) than lymphocytes from young mice, which was also restored by cyclosporin. Oxidized FAD fluorescence was higher in lymphocytes from old mice suggesting a more oxidized state, which may be the cause of the enhanced activation of PT. Incubation of lymphocytes from old mice with the lipophilic cationic dye DiOC6(3), which inhibits electron transport, induced the appearance of apoptotic cells. These findings suggest that the mitochondrial PT is more susceptible to activation in lymphocytes from old mice. This activation may inhibit energy metabolism and enhance apoptosis, and may therefore contribute to immunosenescence.
Rottenberg
H
H
Pathology Department, Allegheny University of the Health Sciences, MCP/Hahnemann School of Medicine, Philadelphia, Pennsylvania 19102, USA. rottenbergh@auhs.edu
Wu
S
S
D000375:Aging / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002232:Carbocyanines / Q000378:metabolism; D005456:Fluorescent Dyes; D007425:Intracellular Membranes / Q000378:metabolism / Q000502:physiology*; D008027:Light; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D010539:Permeability
D002232:Carbocyanines; D005456:Fluorescent Dyes; C007392:3,3'-dihexyl-2,2'-oxacarbocyanine