Speaker: Shijiao Huang, Kansas State University assistant professor in the Department of Biochemistry and Molecular Biophysics

Title: Neural and metabolic regulation of stress resistance and longevity

Abstract: Organisms experience a variety of stresses throughout their lives: cellular stress that triggers molecular intracellular stress responses, physical stress that challenges the whole organism, and psychological stress that involves neurons and hormones. All types of stress perturb homeostasis, leading to either homeostatic imbalance or resilience. In contrast, appropriate activation of stress response pathways leads to improved health indices and lifespan extension. Cell non-autonomous longevity pathways involving neural signaling were initially identified in C. elegans, including insulin-like signaling, dietary restriction, mitochondrial unfolded protein response, endoplasmic reticulum (ER) unfolded protein response, heat shock response, hypoxic response, and are likely to be conserved in more complex organisms. Neural signaling has been reported to be involved in both stress response and longevity. Our goal is to identify neural circuits and their regulated metabolic changes that are central in regulating stress resistance and longevity. We have identified an interneuron involved in the resistance to heat, ER, and mitochondria stress. Ablation of this neuron decreases the levels of total lipids and a poly saturated fatty acid. We also found that knockout of a neuropeptide specifically expressed in this neuron or knockdown of its cognate neuroreceptors increases heat stress resistance. In addition, we also use neuroactive compounds as mechanistic probes to identify neuronal and metabolic targets of lifespan and healthspan extension. We showed that neurotransmitter antagonists extend lifespan, increase motility, and improve short-term and long-term memory in C. elegans. Total lipid levels and fatty acid profiles are remodeled by these neuroactive compounds. We will further explore whether lifespan and cognitive extension are achieved from conserved neurotransmitter-dependent or -independent mechanisms.

Host: Hua Bai, professor in genetics, development and cell biology