[cAMP/PKA signaling underlies age-related memory impairment]

Physiological aging of the brain is inevitable, regardless of the occurrence of pathological diseases such as Alzheimer disease or cerebral vascular disorders. AMI (age-related memory impairment) is an important phenotype of brain aging. In contrast to organismal aging, the molecular mechanisms underlying AMI are poorly understood and hindered by the lack of specific mutants for AMI. We used the fruit fly Drosophila as a novel model for genetic analyses of AMI since it has a short lifespan and is suitable for quantitative analysis of learning and memory. The molecular mechanisms underlying learning and memory in Drosophila are similar to those in mammals. In a screen for AMI mutants, we found that heterozygous mutations of DC0 gene, which encodes the major catalytic subunit of PKA (cAMP-dependent kinase), delayed AMI onset by more than 2-fold without affecting lifespan and memory at young age. The first identification of AMI mutant provides provocative insights into the role of cAMP/PKA signaling and the genetic relationship between organismal aging and brain aging.