Collapse of signal transduction during aging and molecular pharmacological research regarding the control.

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Several different guanine nucleotide regulatory proteins (G proteins) have been identified and their functions explored in brain (e.g.Gsalpha increases adenylyl cyclase and Ca^<2+> channels ; Gi1alpha decreases adenylyl cyclase : Gi2alpha increases phosphatidylinositol-phospholipase C (PI-PLC) ; Gi3alpha increases K^+ channels ; Goalpha decreases Ca^<2+> channels ; Gqalpha increases PI-PLC ; Gbeta decreases adenylyl cyclase and increases PI-PLC). The expression of Gsalpha and beta-actin mRNA was determined over the same period of development by hybridization blot analysis of total mice and rat cerebral cortex RNA using oligonucleotides for probes. Three age groups (3,12 and 24 months old) of male ddy mice and three age groups (3,6 and 24 months old) od male Wistar rats were employed in this study. The mean life spans were 23.1 and 23.5 months in male ddy mice and male Wistar rats, respecively. Total RNA from cerebral cortex was isolated by the guanidinium thiocyanate/phenol/chloroform method. Yield of total RNA/tissue weight did not differ from 3 months to 24 months of age in both animals. An age-dependent increase in the levels of Gsalpha protein mRNA (1.9kb) and beta-actin mRNA (2.0kb) was observed in the mice. In contrast, the levels of Gsalpha mRNA and beta-actin mRNA were essentially identical in the rats during aging. These results indicate that the ontogeny of Gsalpha mRNA and beta-actin mRNA between mice and rats are qualitatively different during brain aging.