Arch. Gerontol. Geriatr., 14 (1992) 131-144 131 © 1992 Elsevier Science Publishers B.V. All rights reserved. 0167-4943/92/$05.00 AC.K~ 00433 In vivo effect of acetyl-L-carnitine on succinate oxidation, adenine nucleotide pool and lipid composition of synaptic and non-synaptic mitochondria from cerebral hemispheres of senescent rats Vittoria Petruzzella a, Loris G, Baggetto b, Francois Penin b, Filomena Cafagna a, Francesca M. Ruggiero a, Palmiro Cantatore a and Maria N. Gadaleta a aDipartimento di Biochimica e Biologia Molecolare e Centro Studi su Mitocondri e Metabolismo Energetico, Universith di Bari, Bari, Italia and hLaboratoire de Biologie et Technologie de Membranes du C. N. R. S, Universitk Claude Bernard, Lyon L France (Received 12 August 1991; revised version received 30 October 1991; accepted 7 November 1991) Summary The effect of acetyl-L-carnitine on succinate oxidation, adenine nucleotide pool and lipid composition of synaptic and 'free', non-synaptic, mitochondria in cerebral hemispheres of senescent rats has been studied. Fisher rats (24- or 28-month-old) were treated with acetyl-L-carnitine (300 mg/kg body wt., in- traperitoneally (i.p.)) 3 h before being killed. Oxygen consumption was measured using succinate as a substrate; adenine nucleotides and lipids were analyzed by high performance liquid chromatography (HPLC). Acetyl-L-carnitine reverses, in synaptic mitochondria, the age-related decrease in the respiratory control ratio due to a higher state 4 respiration rate. Administration of acetyl-L-carnitine to senescent rats does not affect the total adenine nucleotide pool of synaptic and non-synaptic mitochondria which was unchanged with age. Finally, pretreatment of senescent rats with acetyl-L-carnitine brings the cholesterol and phospholipid contents of synaptic mitochondria, reduced in senescent rats, to the adult level; pretreatment of adult rats has no such effect. Altogether these results suggest that acetyl-L- carnitine is able to reverse age-related deficits of brain mitochondria. AcetyI-L-carnitine; Aging brain; Brain mitochondrial respiration; Brain mitochondrial lipid composition Introduction We recently reported (Gadaleta et al., 1990a) that the messenger RNA for the subunit I of cytochrome oxidase (CoI mRNA) and the ribosomal 12S RNA (12S Correspondence to." Prof. Maria Nicola Gadaleta, Department of Biochemistry and Molecular Biology, Tray. 200 Re David, 4 70125 Bari, Italy.