ABSTRACT

Impaired mitochondrial function is often considered to be a factor contributing to aging in post-mitotic tissues. However, there is considerable evidence that liver mitochondria also undergo age-related changes that may impact function. There is also evidence that mitochondrial and cristae numbers are decreased and mitochondrial volume is increased in hepatocytes with aging. Several studies have shown that mitochondrial

Abstract .................................................................................................................. 141 Introduction ............................................................................................................ 142 Mitochondrial Number and Morphology ............................................................... 142

Aging ................................................................................................................. 142 Calorie Restriction ............................................................................................ 144

Mitochondrial Respiration ..................................................................................... 145 Aging ................................................................................................................. 145 Calorie Restriction ............................................................................................ 148

Mitochondrial Membrane Potential and Proton Leak ............................................ 148 Aging ................................................................................................................. 148 Calorie Restriction ............................................................................................ 150

Electron Transport Chain Enzymes ....................................................................... 151 Aging ................................................................................................................. 151 Calorie Restriction ............................................................................................ 154

Oxidative Stress ..................................................................................................... 155 Aging ................................................................................................................. 155 Calorie Restriction ............................................................................................ 158

Fatty Acid Composition ......................................................................................... 159 Aging ................................................................................................................. 159 Calorie Restriction ............................................................................................ 159

Conclusion ............................................................................................................. 160 References .............................................................................................................. 160

respiration and membrane potential are decreased in hepatocytes from old versus young animals. Mitochondrial proton leak, reactive oxygen species production, and oxidative damage to mitochondrial macromolecules are increased with aging in liver. Furthermore, mitochondrial membrane fatty acid composition is altered with aging in a manner that increases susceptibility to peroxidation. Calorie restriction (CR) opposes many of these age-related changes in liver mitochondria. In particular, CR prevents age-related decreases in the number of mitochondria and cristae. There is also evidence that CR opposes age-related increases in mitochondrial proton leak and oxidative damage. Age-related changes in liver mitochondria are consistent with the idea that impaired mitochondrial function could contribute to liver aging.