• Modulating neuronal aging: insights from insulin signaling genes and Alaskan nutraceuticals

      Scerbak, Courtney; Taylor, Barbara; Podlutsky, Andrej; Harris, Michael; Dunlap, Kriya; Driscoll, Monica; Vayndorf, Elena (2016-05)
      While aging impacts most, if not all, living organisms, the molecular mechanisms behind this phenomenon are not completely understood. Here, I aimed to further describe the intricate relationship between genetics and diet in aging, focusing on touch receptor neuron aging processes in the model nematode, Caenorhabditis elegans. I specifically tested the hypotheses that (1) age-related touch receptor neuron morphological changes are associated with whole organism health, (2) intrinsic (i.e. genetic) and extrinsic (i.e. nutritional) factors can influence these morphological changes, and (3) specific cellular signaling processes underlie these morphological changes. To this end, this dissertation has three components: (1) the impact of insulin signaling disruption on neuron morphology and protein aggregation in a model of Huntington’s Disease; (2) establishment of Alaskan nutraceutical treatments that extend lifespan and offset age-related decline in neuron and whole organism health; and (3) description of mechanisms driving Alaskan nutraceutical treatment effects using RNA sequencing to target subsequent experiments. In all three of these components, I measured markers of whole organism health (e.g. lifespan, motility, endogenous reactive oxygen species) and markers of touch receptor neuron health (e.g. neuron morphology, mechanosensation). Together, this dissertation demonstrated that lifespan-extending interventions (e.g. decreased insulin signaling, Alaskan nutraceutical treatments) improved mechanosensation and, interestingly, differentially modulated development of age-related neuron morphological changes. That beneficial treatments increased the occurrence of posterior neuron process branching and/or decreased the occurrence of several anterior cell soma morphologies (e.g. soma outgrowths) suggests that some morphologies are representative of successful defense of the cell against age-related deterioration, while others are markers of cellular dysfunction. These results support the idea that multiple cellular signaling pathways are involved in aging of touch receptor neurons, and thus, there are multiple mechanisms for promoting health with age at the cellular level.