Genes for age-related cognitive decline found in adult worm neurons

Genes for age-related cognitive decline found in adult worm neurons

The small soil-dwelling roundworm, Caenorhabditis elegans, contains genes that determine the rate of aging and overall health during aging. Mutations in one of these genetic pathways, the insulin/IGF-1 signaling (IIS) pathway, can double worm lifespan. Similar mutations in humans have been found in long-lived humans.

But studying the IIS mutation in adult worm neurons was difficult because the adults have a thick, durable covering that protects the neurons.

Using a new technique they developed to break up the tough outer covering, researchers at Princeton succeeded in isolating adult neurons, which enabled the detection of the new set of genes regulated by the insulin/IGF-1 signaling pathway.

One of the newly identified genes, fkh-9, regulates both enhanced memory and neuronal regeneration in IIS mutants. The researchers also found that fkh-9 gene expression is required for long lifespan in many IIS mutants, but it did not play that role in neurons, suggesting the gene governs multiple outcomes in the worm.

The gene codes for a protein, FKH-9, that acts as a transcription factor, meaning it controls the expression of other genes and is likely part of a larger regulatory network. FKH-9 also appears to regulate different processes in different tissues: It is required in neurons for memory and axon repair, but not for lifespan.