CALORIC RESTRICTION RETARDS THE AGING-ASSOCIATED CHANGES IN GAMMA-AMINOBUTYRIC ACID(A) 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 bene ficial effects exerted by dietary manipulation may be due to a direct effect at the molecular level like gene expression. The studies were c onducted to determine whether calorie restriction prevents any age-rel ated 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 reduc ed in the cerebellum. In contrast, [S-35]TBPS binding remained unchang ed in the cerebellum of calorie restricted old rats. In order to evalu ate the molecular basis of these changes, the alpha sub-unit mRNA leve ls were measured. The GABA(A) receptor alpha(1) sub-unit mRNA level re mained 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 cerebe llum of calorie restricted old animals. These findings indicate a sele ctive age and diet related modulation in the stoichiometry of the GABA (A) receptor in aging. (C) 1998 Elsevier Science B.V.