Figure 1: Mitochondria in aging neurons show decline from their young counterparts in a range of functional areas. (A) Antioxidant homeostasis: aged mitochondria produce excessive reactive oxygen species and show decreased antioxidant capability, leading to oxidative stress. (B) Bioenergetics: aged mitochondria exhibit decreased ability to efficiently and effectively meet the high energy demand of the cell especially in the growing axon. (C) Transmembrane transport: decreased expression and/or function of transmembrane transport channels in aged mitochondria may result in decreased transport of essential molecules into the matrix and impaired protein turn-over. (D) Calcium buffering and the mitochondrial permeability transition pore (mPTP): with increased ROS and an oxidative stress state the mPTP in aged mitochondria is more active and shows prolonged opening, effecting calcium buffing ability and contributing to mitochondrial membrane depolarization. All of these elements are detrimental to neuronal health and may contribute to the age-dependent decline in axon growth potential. ADP: Adenosine diphosphate; ATP: adenosine triphosphate; C: cytoplasm; CI-CV: OXPHOS complex 1–5; Δφ: membrane potential; IM: inner membrane; IMS: inter-membrane space; M: mitochondrial matrix; mPTP: mitochondrial permeability transition pore; OM: outer membrane; ROS: reactive oxygen species; TIM: translocase inner membrane; TOM: translocase outer membrane.