ACETYL-L-CARNITINE FED TO OLD RATS PARTIALLY RESTORES MITOCHONDRIAL-FUNCTION AND AMBULATORY ACTIVITY

Mitochondrial function and ambulatory activity were monitored after fe eding old rats acetyl-L-carnitine (ALCAR). Young (3-5 mo) and old (22- 28 mo) rats were given a 1.5% (wt/vol) solution of ALCAR in their drin king water for 1 mo, were sacrificed, and their liver parenchymal cell s were isolated. ALCAR supplementation significantly reverses the age- associated decline of mitochondrial membrane potential, as assessed by rhodamine 123 staining. Cardiolipin, which declines significantly wit h age, is also restored. ALCAR increases cellular oxygen consumption, which declines with age, to the level of young rats. However, the oxid ant production per oxygen consumed, as measured by 2',7'-dichlorofluor escin fluorescence levels, is approximate to 30% higher than in untrea ted old sees. Cellular glutathione and ascorbate levels were nearly 30 % and 50% lower, respectively, in cells from ALCAR-supplemented old ra ts than in untreated old rats, further indicating that ALCAR supplemen tation might increase oxidative stress. Ambulatory activity in young a nd old rats was quantified as a general measure of metabolic activity, Ambulatory activity, defined as mean total distance traveled, in old rats is almost 3-fold lower than in young animals. ALCAR supplementati on increases ambulatory activity significantly in both young and old r ats, with the increase being larger in old rats. Thus, ALCAR supplemen tation to old rats markedly reverses the age-associated decline in man y indices of mitochondrial function and general metabolic activity, bu t may increase oxidative stress.