Grant: Project Grant

Throughout their lifespan, organisms encounter a wide variety of external and internal stressors. The ability to survive and recover from these stressors is known as biological resilience. Our previous research has demonstrated a strong relationship between resilience, lifespan and neurodegenerative disease. As organisms age, their ability to resist stress decreases, while their susceptibility to neurodegenerative disease increases. Genes and interventions that delay aging in model organisms tend to increase resistance to stress and protect against neurodegeneration. Our recent work shows a significant, positive correlation between lifespan and resilience resulting from the same underlying genetic pathways contributing to both phenotypes. Our work further indicates that this relationship is causal, as disruption of pathways of cellular resilience decreases lifespan. In this work, we will define the relationship between biological resilience, aging and neurodegenerative disease. We will (1) identify the genes that are modulated by different pathways of cellular resilience in response to external stressors and define how different pathways of cellular resilience act together; (2) identify genes that individually contribute to biological resilience; and (3) determine the extent to which established pathways of cellular resilience can extend longevity and protect against neurodegenerative disease. This knowledge will be beneficial in promoting healthy aging and developing new treatments against neurodegenerative disease.