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

PLoS Biol. 2010 May 18;8(5):e1000372. doi: 10.1371/journal.pbio.1000372.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology*
  • Animal Feed*
  • Animals
  • Association Learning
  • Behavior, Animal
  • Caenorhabditis elegans / physiology
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Chemotaxis
  • Cyclic AMP Response Element-Binding Protein / genetics
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Humans
  • Insulin / metabolism*
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism
  • Learning / physiology*
  • Memory / physiology*
  • Mutation
  • Receptor, Insulin / genetics
  • Receptor, Insulin / metabolism
  • Receptors, Nicotinic / genetics
  • Receptors, Nicotinic / metabolism
  • Signal Transduction*

Substances

  • Caenorhabditis elegans Proteins
  • Cyclic AMP Response Element-Binding Protein
  • Eat-2 protein, C elegans
  • Insulin
  • Receptors, Nicotinic
  • Insulin-Like Growth Factor I
  • DAF-2 protein, C elegans
  • Receptor, Insulin