Xuebing Wu, PhD

Aging as a self-reinforcing feedback loop: investigate the role of noncoding translation

Natural aging is characterized by unidirectional deterioration of cellular homeostasis. In both engineering and biological systems, unidirectional processes are often driven by positive feedback loops that can reinforce an initial perturbation and push a system towards extreme states. We aim to test the hypothesis that natural aging as a unidirectional process is driven by a self-reinforcing feedback loop that amplify errors in three fundamental processes of gene expression: defects in RNA processing (i.e., splicing and polyadenylation), translation of noncoding sequences (i.e., introns, UTRs, and lncRNAs), and disruption of protein homeostasis (proteostasis). By utilizing aging mouse brains as a model system, we will employ systems biology approaches to investigate the crosstalk among these cellular processes at the genome scale and assess a causal relationship between aging and this feedback loop.