Insulin signaling and dietary restriction differentially influence the decline of learning and memory with age

Of all the age-related declines,memory loss is one of the most devastating. while conditions that increase longevity have been identified,the effects of these longevity-promoting factors on learning and memory are unknown. here we show that the c. elegans insulin/igf-1 receptor mutant daf-2 improves memory performance early in adulthood and maintains learning ability better with age but,surprisingly,demonstrates no extension in long-term memory with age. by contrast,eat-2 mutants,a model of dietary restriction (dr),exhibit impaired long-term memory in young adulthood but maintain this level of memory longer with age. we find that crh-1,the c. elegans homolog of the creb transcription factor,is required for longterm associative memory,but not for learning or short-term memory. the expression of crh-1 declines with age and differs in the longevity mutants,and creb expression and activity correlate with memory performance. our results suggest that specific longevity treatments have acute and long-term effects on cognitive functions that decline with age through their regulation of rate-limiting genes required for learning and memory. © 2010 kauffman et al.