Caenorhabditis elegans

Caenorhabditis elegans validated in a multicellular animal what yeast research suggested: caloric restriction extends lifespan through conserved molecular mechanisms. This tiny nematode worm—exactly 959 somatic cells in adults—became the crucial bridge between single-celled yeast and complex organisms. When C. elegans mutants in the daf-2 insulin receptor pathway lived twice as long as normal worms, aging research transformed from describing inevitable decline to manipulating specific genetic circuits.

The elegance of C. elegans for aging research stems from practical advantages. Adults live only 2-3 weeks, enabling rapid experiments. The transparent body allows visualization of cellular processes in living animals. The fully mapped cell lineage means researchers know exactly which cell becomes what. Complete RNAi libraries enable systematic gene knockdown. These technical features, combined with conserved aging pathways, made C. elegans the system where longevity genetics became experimentally tractable.

C. elegans research revealed the insulin/IGF-1 signaling (IIS) pathway as a master regulator of lifespan. Reducing IIS activity—through genetic mutation or dietary restriction—activates stress responses, alters metabolism, and dramatically extends life. The downstream transcription factor DAF-16/FOXO directly regulates hundreds of genes affecting longevity. These discoveries translated to other species: the same pathways influence lifespan in flies, mice, and likely humans. The worm served as a genetic filter, identifying pathways that evolution preserved for hundreds of millions of years.