Acute changes in PKA activity at old ages shifts memory retention curves between young and old states. A, Wild-type flies show characteristic changes in the shape of their memory retention curves upon aging. One hour memory is severely reduced, while 3 min memory (0 h) and 7 h memory are only mildly affected. Two-way ANOVA indicates significant differences in memory due to retention time (p < 0.0001), age (p < 0.0001), and interaction between age and retention time (p = 0.0011). Bonferroni post hoc analyses demonstrate a slight but significant decrease in 3 min memory between 1-d-old and 25-d-old flies (*p < 0.05) and a larger decrease in 1 h memory between 1-d-old and 20-d-old (**p < 0.001) and 25-d-old (**p < 0.001) flies. B, Flies from a DC0B3/+ background do not show AMI and maintain youthful memory up to 25 d of age. Acute induction of a DC0 transgene in B3/+;MBS/DC0+ flies (feeding RU486 from 23 to 25 d of age) shifts the retention curve to that of old wild-type flies. Two-way ANOVA indicates significant differences due to retention time (p < 0.0001), age and drug treatment (p < 0.0001), and the interaction between retention time and age and drug treatment (p = 0.0041). Bonferroni post hoc analyses do not demonstrate any significant differences in memory between 1-d-old and 25-d-old B3/+;MBS/DC0+ non-drug-treated flies, but they do demonstrate significant changes in 1 h and 7 h memory upon acute treatment with RU486 (**p < 0.001 in both cases comparing 25-d-old RU486-treated flies to both 1-d-old and 25-d-old non-drug-treated flies). C, PKI;;MBS flies show normal AMI in the absence of RU486 feeding. Acute inhibition of PKA by feeding RU486 at 18–20 d of age suppresses AMI and shifts the memory retention curve to that of young flies. Two-way ANOVA indicates significant differences due to retention time (p < 0.0001), age and drug treatment (p < 0.0001), and the interaction between retention time and age and drug treatment (p = 0.0139). Bonferroni post hoc analyses demonstrate a significant difference in 1 h memory between 1-d-old and non-drug-treated 20-d-old PKI;;MBS flies (**p < 0.001). This difference is abolished when PKI;;MBS flies are acutely fed RU486 from 18 to 20 d of age. N = 8–12 for all data.