Modulation of Mitochondrial Function in Elderly Brain: Involvement of Autophagy and Apoptosis

Abstract

Mitochondria are crucial cellular organelles that regulate energy production, oxidative balance, and calcium homeostasis, among other things. Aging is a natural, multifactorial, and multi-organic process, in which both pathological and physiological changes occur gradually over time. Autophagy capacity and mitochondrial processes such as mitophagy, biogenesis, and dynamics are associated with aging. These processes are important for maintaining the structural integrity of mitochondria and thus cell life since mitochondrial dysfunction leads to an impairment in energy metabolism and an increased production of reactive oxygen species, both of which may stimulate mechanisms of cellular senescence and apoptotic cell death. Furthermore, in both model organisms and humans, a decline in mitochondrial activity can contribute to age-related disease phenotypes. As people age, mitochondrial damage and malfunction may induce apoptosis, thus explaining the rise in cell death. Many aging processes are believed to be driven by oxidative stress. Taken together, the evidence strongly suggests a relation between mitochondrial function and a wide spectrum of aging processes. Although there is no general consensus among the studies reviewed, it appears that aging reduces mitochondrial biogenesis and dynamics, as well as the mitophagy capacity of the organism involved. This review describes the involvement of autophagy and apoptosis in the modulation of mitochondrial function in the brain.