Postdoctor Researcher Jeju National University, Republic of Korea
Abstract: Aging is characterized by a gradual decline in physiological functions, with notable changes in the central nervous system accompanied by hyperactivation of hypothalamus-pituitary-adrenal (HPA) axis. Stress resilience, the ability to adapt to and recover from stress, is influenced by both environmental and genetic factors, which can reduce the risk of stress-induced disorders such as Alzheimer’s disease (AD) and depression. Consequently, resilience has emerged as a critical factor in alleviating HPA axis dysregulation, which mitigates the aging process. However, stress resilience is a complex and multifaceted trait influenced by subjective experience, genetic predisposition, and environmental interactions, making it difficult to assess human stress resilience. Therefore, in this study, we exposed mice with Chronic Unpredictable Mild Stress (CUMS) model which usually impairs cognitive and mood regulation in mice. We then identified resilient mice maintaining behavior similar to the control group in the tail suspension test and Y-maze test, while susceptible group exhibited both cognitive deficits and depression-like behaviors. Also, we performed total RNA sequencing and Assay for Transposase-Accessible Chromatin using sequencing (ATAC) sequencing to identify genes associated with stress resilience and further evaluated their ani-aging effects. We further assessed the neuroprotective effects of these genes in an aging animal model. This study highlights the molecular mechanisms underlying resilience and suggests that targeting resilience pathways may offer novel therapeutic strategies for delaying aging and maintaining neural health.
