Brain mitochondrial dysfunction in aging

Abstract

Aging of mammalian brain is associated with a continuous decrease of the capacity to produce ATP by oxidative phosphorylation. The impairment of mitochondrial function is mainly due to diminished electron transfer by complexes I and IV, whereas inner membrane H+ impermeability and F1-ATP synthase activity are only slightly affected. Dysfunctional mitochondria in aged rodents show decreased rates of respiration and of electron transfer, decreased membrane potential, increased content of the oxidation products of phospholipids and proteins, and increased size and fragility. In aging mice, the activities of brain mitochondrial enzymes (complexes I and IV and mtNOS) are linearly correlated with neurological performance (tightrope and T-maze tests) and with median life span and negatively correlated with the mitochondrial content of lipid and protein oxidation products. Conditions that increased mice median life span, such as moderate exercise, vitamin E supplementation, caloric restriction, and high spontaneous neurological activity; also improved neurological performance and mitochondrial function in aged brain. The diffusion of mitochondrial NO and H2O2 to the cytosol is decreased in the aged brain and may be a factor for reduced mitochondrial biogenesis.