Mitochondrial dysfunction in brain aging: role of oxidative stress and cardiolipin

Aging is a biological process characterized by impairment of cellular bioenergetic function, increased oxidative stress, attenuated ability to respond to stresses, increased risk of contracting age-associated disorders that affects many tissues, with a more marked effect on brain and heart function. Oxidative stress is widely thought to underpin many aging processes. The mitochondrion is considered the most important cellular organelle to contribute to the aging process, mainly through respiratory chain dysfunction and formation of reactive oxygen species, leading to damage to mitochondrial proteins, lipids and mitochondrial DNA. Furthermore, exposure to oxidants, especially in the presence of Ca(2+), can induce the mitochondrial permeability transition with deleterious effects on mitochondrial function. Cardiolipin plays a central role in several mitochondrial bioenergetic processes as well as in mitochondrial-dependent steps in apoptosis and mitochondrial membrane stability and dynamics. Alterations to cardiolipin structure, content and acyl chain profile have been associated with mitochondrial dysfunction in multiple tissues in several physiopathological conditions and aging. In this review, we focus on the role played by oxidative stress and cardiolipin in mitochondrial bioenergetic alterations associated with brain aging.