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

TitleInsulin signaling and dietary restriction differentially influence the decline of learning and memory with age.
Publication TypeJournal Article
Year of Publication2010
AuthorsKauffman AL, Ashraf JM, M Corces-Zimmerman R, Landis JN, Murphy CT
JournalPLoS Biol
Volume8
Issue5
Paginatione1000372
Date Published2010 May 18
ISSN1545-7885
KeywordsAging, Animal Feed, Animals, Association Learning, Behavior, Animal, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Chemotaxis, Cyclic AMP Response Element-Binding Protein, Humans, Insulin, Insulin-Like Growth Factor I, Learning, Memory, Mutation, Receptor, Insulin, Receptors, Nicotinic, Signal Transduction
Abstract

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.

DOI10.1371/journal.pbio.1000372
Alternate JournalPLoS Biol.
Full Text
PubMed ID20502519
PubMed Central IDPMC2872642
Grant ListR01 AG034446 / AG / NIA NIH HHS / United States
1R01AG034446-01 / AG / NIA NIH HHS / United States