Aging is a complex biological process that affects organisms ranging from humans to yeast, and understanding this process holds great potential for reducing the impact of age-related diseases such as heart disease, cancer, and neurodegenerative diseases. In this dissertation I explore both how neurons regulate lifespan and how two genes fundamental to the aging process interact with each other. First, I explore the neuronal regulation of lifespan. While we know that altering neuronal function can alter lifespan, the specific mechanisms by which neurons affect these changes, especially at the level of neuronal communication, remain to be elucidated. I show that reduction in signaling of the C. elegans ASI gustatory neuron pair through chemical silencing with tetanus toxin extends lifespan, likely primarily through reducing secretion of a TGFβ ligand (DAF-7), inhibiting the insulin-like signaling pathway, and activating the transcription factor DAF-16. Further results, such as a partial independence from daf-16, hint at a neuronal regulation of lifespan more complex than a sensory dial which increases or reduces DAF-7 levels.
Second, I explore how the developmental arrest caused by reduction of activity of the fundamental lifespan gene heat shock factor 1 (hsf-1) can be rescued by loss of function of another gene, the ribosomal S6 kinase gene rsks-1. hsf-1, a regulator of the widely conserved heat-shock response, is not only essential for cellular stress resistance and adult longevity, but also for proper development. However, the genetic mechanisms by which heat-shock transcription factors regulate development are not well understood. I investigated how C. elegans strains derived from an unbiased genetic screen ameliorated the developmental-arrest phenotype of a heat-shock factor mutant. Here I show that loss of the conserved translational activator rsks-1/S6 Kinase, a downstream effector of mTOR kinase, can rescue the developmental-arrest phenotype of hsf-1 partial loss-of-function mutants. Unexpectedly, I show that the rescue is not likely caused by reduced translation, nor by activation of any of a variety of stress-protective genes and pathways. My findings identify an as-yet unexplained regulatory relationship between the heat-shock transcription factor and the mTOR pathway during C. elegans’ development.