65 - Age-dependent Decline in Adaptive Homeostasis and Nrf2 Mediated Proteasome Induction in Human Bronchial Epithelial Cells Exposed to Oxidative Stress

Abstract

The proteasome plays a large role in maintaining protein homeostasis, the loss of which is a hallmark of aging. Adaptive homeostasis, which is the transient modulation of the homeostatic range in response to non-damaging levels of a stressor such as free radicals generated from oxidative stress, is likewise diminished by aging. This adaptive response, which has been clearly defined in many model organisms and cell lines, has rarely been examined in primary cells, and never in Human Bronchial Epithelial cells (HBEs). These cells are continually exposed to higher oxygen levels (relative to many other cell types) and offer an interesting perspective on the impact of chronic exposure to higher levels of oxygen on the adaptive response. Results indicate HBEs from a young donor exhibit a strong adaptive response associated with the presence of the proteasome regulator, Nrf2. Preliminary results also show a trend of diminishing adaptive response and Nrf2 levels from several older donors. These results point to an interesting avenue for future HBE studies investigating age and/or sex-related changes in adaptive responses in primary cells from males and females of different ages, with and without various diseases.