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 long-term 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.
Kauffman
Amanda L
AL
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America.
Ashraf
Jasmine M
JM
Corces-Zimmerman
M Ryan
MR
Landis
Jessica N
JN
Murphy
Coleen T
CT
D000375:Aging / Q000502:physiology*; D000821:Animal Feed; D000818:Animals; D001245:Association Learning; D001522:Behavior, Animal; D017173:Caenorhabditis elegans / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002633:Chemotaxis; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D007858:Learning / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D009154:Mutation; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
D029742:Caenorhabditis elegans Proteins; D017362:Cyclic AMP Response Element-Binding Protein; C487508:Eat-2 protein, C elegans; D007328:Insulin; D011978:Receptors, Nicotinic; D007334:Insulin-Like Growth Factor I; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin