The effects of long-term carnitine supplementation on age-related changes in tissue carnitine levels and in lipid metabolism were investigated. The total carnitine levels in heart, skeletal muscle, cerebral cortex, and hippocampus were ‫ف‬ 20% less in aged rats (22 months old) than in young rats (6 months old). On the contrary, plasma carnitine levels were not affected by aging. Supplementation of acetyl-l -carnitine (ALCAR; 100 mg/kg body weight/day for 3 months) significantly increased tissue carnitine levels in aged rats but had little effect on tissue carnitine levels in young rats. Plasma lipoprotein analyses revealed that triacylglycerol levels in VLDL and cholesterol levels in LDL and in HDL were all significantly higher in aged rats than in young rats. ALCAR treatment decreased all lipoprotein fractions and consequently the levels of triacylglycerol and cholesterol. The reduction in plasma cholesterol contents in ALCAR-treated aged rats was attributable mainly to a decrease of cholesteryl esters rather than to a decrease of free cholesterol. Another remarkable effect of ALCAR was that it decreased the cholesterol content and cholesterol-phospholipid ratio in the brain tissues of aged rats. These results indicate that chronic ALCAR supplementation reverses the age-associated changes in lipid metabolism. Aging causes quantitative and compositional changes in body lipids. Analyses of plasma samples from humans and experimental animals indicate that cholesterol and triacylglycerol levels increase with aging (1-3). Aging increases total cholesterol and decreases phospholipids, leading to increased cholesterol-phospholipid molar ratios in hepatic mitochondria (4), brain (5), and cerebral synaptic membranes (6). These age-related changes in lipid composition in various tissues and organs are thought to account not only for the age-related accumulation of body fat, which is a risk factor for diabetes and atherosclerotic diseases, but also for age-related cellular hypofunction. Therefore, reversing age-related changes in lipid metabolism would help to maintain normal cellular function and prevent common diseases.Carnitine plays an essential role in transporting fatty acids into mitochondria, where they are oxidized to produce energy in tissues (7). Carnitine levels in cardiac and skeletal muscles, both of which are major storage sites of carnitine, appear to decrease with age (8-11). In plasma, however, it is unclear whether carnitine levels decease with age. Some studies have shown an increase in plasma carnitine levels with aging (12, 13), whereas others have found significant decreases in human (14) and rat (10). This inconsistency is a problem because plasma carnitine levels are often used as an index of body carnitine status. Concerning the age-related changes in carnitine levels in tissues and organs, cardiac and skeletal muscles have frequently been investigated (8-11), but other organs have not attracted much attention. One study reported a decrement of carnitine contents in the brain and a drast...