Research fellow Mayo Clinic Phoenix, Arizona, United States
Abstract Text:
Introduction: Cellular senescence, an irreversible growth arrest, plays a crucial role in aging and related diseases. In T cells, senescence leads to functional decline, contributing to immune senescence. This study aims to explore the links between senescence and mitochondrial function in T cells to better understand immune aging. We designed a flow cytometry panel to investigate these associations.
Methods: Senescence was characterized in peripheral blood from >65-year-old individuals (n=9) using flow cytometry. Our panel assessed senescence, activation, cellular stress and DNA damage markers. Additionally, we evaluated Senescence-Associated β-Galactosidase (SA-β-gal), mitochondrial mass, membrane potential, and Reactive Oxygen Species (DCFDA) to assess immune cell functionality and metabolism.
Results: A reverse correlation was found between DCFDA+ and SA-β-Gal+ populations in Non-Treg cells (r = -0.78, p = 0.01), indicating an interplay between oxidative stress and senescence. In CD4+ populations, CD28+ cells inversely correlated with Mitotracker (r = -0.85, p = 0.003), suggesting a link between CD28 expression, mitochondrial mass, and T cell function. Furthermore, H2AX, a marker for mitochondrial damage, inversely associated with TMRE in CD4+ cells, indicating a potential link between DNA damage and mitochondrial function.
Discussion: These findings shed light on regulatory mechanisms governing senescence and mitochondrial dynamics in T cell subsets. Understanding these associations may lead to targeted interventions to mitigate immune aging and enhance immune function, particularly in elderly patients. This flow cytometry panel offers potential for assessing senescence in various disorders.
