Characterizing the Molecular and Cellular Changes of Senescent Cells Induced by Diverse Stressors in 2D and 3D Microenvironments

Aging is a risk factor for myriad diseases and is often associated with the accumulation of senescent cells. Cellular senescence, a process of irreversible cell cycle arrest, is associated with various changes in cellular morphology and function. While senescence will occur naturally in a time-dependent manner, it can be prematurely induced by various extrinsic and intrinsic factors. Most senescence studies model cell behavior in two-dimensional (2D) microenvironments; however, these models are not physiologically relevant. In this study, the effects of naturally occurring reactive oxygen species (ROS) hydrogen peroxide (H2O2) and commonly used chemotherapy drugs, doxorubicin and palbociclib, on cellular senescence are modeled and compared in 2D and 3D replicas of skin tissue using human foreskin fibroblasts (HFF). This study shows that senescence associated cellular changes are not only stressor-dependent, but also environment dependent.