Caloric restriction retards the aging associated changes in γ-aminobutyric acidA receptor gene expression in rat cerebellum

It is widely accepted that calorie restriction is an effective way of delaying the aging process. Also, there is an indication that the beneficial effects exerted by dietary manipulation may be due to a direct effect at the molecular level like gene expression. The studies were conducted to determine whether calorie restriction prevents any age-related changes in the structural and molecular aspects of the GABA(A)-BZ receptor. In aged (24-month old diet ad Libitum) rats, the binding of [S-35]t-butyl-bicyclophosphorothionate (TBPS) was significantly reduced in the cerebellum. In contrast, [S-35]TBPS binding remained unchanged in the cerebellum of calorie restricted old rats. In order to evaluate the molecular basis of these changes, the alpha sub-unit mRNA levels were measured. The GABA(A) receptor alpha(1) sub-unit mRNA level remained unchanged in both the old groups of rats. The alpha(2) subunit mRNA level was significantly decreased in the cerebellum of aged rats (24-month old ad libitum), whereas it remained unchanged in the cerebellum of calorie restricted old animals. These findings indicate a selective age and diet related modulation in the stoichiometry of the GABA(A) receptor in aging. (C) 1998 Elsevier Science B.V.