Abstract
Age-related impairment (AMI) is one of the functional senescence of brain and does not accompany pathological symptom. Previously, we have identified that DC0 mutation is a suppressor of AMI in Drosophila. DC0 gene encodes a PKA (cAMP-dependent kinase) catalytic subunit preferentially expressed in the mushroom bodies (MBs), essential structures for olfactory learning and memory. Heterozygous mutations of DC0 gene, DC0/+, delay AMI more than two-fold without affecting lifespan. PKA activity in DC0/+ mutant is reduced to ∼60% of that in wild-type flies. Furthermore inhibition of PKA activity in the MBs of wild-type flies also suppresses AMI, indicating that activity of cAMP/PKA leads to AMI. Prevailing model of aging propose that functional senescence is caused by an accumulating processes such as by reactive oxygen species and insulin signaling. Using temporally and spatially restricted induction system of transgene, we here examined whether accumulative activity of cAMP/PKA signaling during aging is a causal factor of AMI. Surprisingly, in addition to constitutive expression of DC0 transgene during aging, AMI was restored in DC0/+ flies when DC0 transgene was acutely induced at old age. Furthermore, when induction of DC0 transgene was ceased in DC0/+ flies at old age, their memory was improved to young control level. These results demonstrate that activity of cAMP/PKA at old age, but not cumulative activity, gives rise to AMI. [J Physiol Sci. 2008;58 Suppl:S113]
