Age-related memory impairment (AMI), also called aging associated memory impairment, is a normal condition observed in a wide variety of species from Caenorhabditis elegans to human. AMI occurs unexpectedly early during the reproductive phase, which may be a tradeoff relevant to evolution. An important but frequently missed concept is that the early phase of AMI is associated with reduced memory of new information but also with well-retained memory of certain old information, leading to a shift of behavioral plasticity. Early AMI affects short-term memory and long-term memory, which are modulated by the serotonin pathways, the insulin/insulin-like growth factor 1 pathway, and the genes involved in memory formation. This chapter describes the current understanding of AMI and clarifies misunderstandings in this emerging field of C. elegans AMI. It discusses the “middle-life crisis” theory that can apply to cognitive aging, including endocrine and epigenetic changes.
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