Fig. 8. A working model of mitochondrial senescence [65].

Replicative senescence induces metabolic changes in mitochondria evident as accumulation of ROS, shutdown of TCA and ETC pathways, glutathione depletion, and energy exhaustion. ROS, reactive oxygen species; ETC, electron transport chain; PFK, phosphofructokinase; LDH, lactate dehydrogenase; GP, glycogen phosphorylase; H₂O₂, hydrogen peroxide; SA, superoxide anions; LPO, lipid peroxides; PCC, protein carbonyl content; GSSG, oxidized glutathione; TrxR2, thioredoxin reductase 2; SOD2, superoxide dismutase 2; GPx1, glutathione peroxidase 1; GR, glutathione reductase; GSH, reduced glutathione.