MITOCHONDRIAL DYSFUNCTION IN LYMPHOCYTES FROM OLD MICE - ENHANCED ACTIVATION OF THE PERMEABILITY TRANSITION

Aging is associated with mitochondrial dysfunction in excitable tissue s such as nerve and muscle. However, it is not known if immunosenescen ce is similarly associated with mitochondrial dysfunction in lymphocyt es, We have found that spleen lymphocytes from old mice have lower res piration rates than lymphocytes from young mice, Cyclosporin, an inhib itor of the mitochondrial Permeability Transition, PT, restored normal respiration rates to lymphocytes from old mice, suggesting enhanced s usceptibility to PT activation. Lymphocytes from old mice also had a l ower 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 cation ic dye DiOC(6)(3), which inhibits electron transport, induced the appe arence of apoptotic cells. These findings suggest that the mitochondri al PT is more susceptible to activation in lymphocytes from old mice. This activation may inhibit energy metabolism and enhance apoptosis, a nd may therefore contribute to immunosenescence. (C) 1997 Academic Pre ss.