The effect of age and caloric-restriction (CR) diet on mitochondrial DNA (mtDNA) content in different rat tissues was investigated. A decrease of the mtDNA content occurs with aging in liver and soleus muscle, whereas there is no age-related significant change of mtDNA content in brain. CR fully reverses the age-dependent loss of mtDNA in liver and soleus, whereas it results in a significant increase of mtDNA amount above the value of aged ad libitum fed rats in brain. These results further support the tissue-specific effect of CR, likely because of the different dependence of tissues on external nutrient uptake.