Decline in respiratory control ratio of rat liver mitochondria in old age.

Rat liver mitochondria isolated from old animals (27-33 months) showed a clear decline in the state 3 rate of respiration (presence of ADP) compared with mitochondria from mature animals (3-12 months) when using either succinate or NAD+-linked substrates. The state 4 rate of respiration (absence of ADP), which is a sensitive indicator of damage to the inner mitochondrial membrane, remained unchanged. Consequently the respiratory control ratio (state 3/state 4) declined. A loss of reserve capacity to maintain the ADP:O ratio was also observed. These observations indicate a decline in energy production in old animals.