CARNITINE PALMITOYL TRANSFERASE-I ACTIVITY IN THE AGING MOUSE HEART

We investigated the influence of age on carnitine palmitoyl transferase-I (CPT-I, EC 2.3.1.21) activity in the mouse heart. There was an age-associated decrease in CPT-I activity from 2 to 26 months (P = 0.006). We studied the effect of oxygen-derived radicals on CPT-I activity. Mitochondria from 2-month-old mouse hearts exposed to different concentrations of hydrogen peroxide (H2O2) showed a dose-related decrease in CPT-I activity (P < 0.002). To determine the possible reversibility of the age change in CPT-I activity, we studied the effect of oral administration of propionyl-L-carnitine (PLC). Oral pretreatment of middle-aged (18-month-old) mice with PLC resulted in a 37% increase of basal CPT-I activity (P < 0.05) compared to age-matched untreated animals, and restored it to a level similar to that of 2-month-old mice. Pretreatment of senescent (26-month-old) mice with PLC, however, showed no significant change in basal CPT-I activity. It is possible that the age-related decrease in CPT-I activity may result from an in vivo accumulation of oxygen-derived radical damage. It appears that the age change in CPT-I activity in 18- but not in the 26-month-old mice is reversible with PLC.