Cellular senescence is a response to stress in which cells exit the cell cycle and neither proliferate nor apoptose. This state can be viewed as a “double-edged sword” with both positive and negative effects on the body. Senescence helps to combat cancer by preventing excess cell growth, yet an accumulation of dysfunctional cells can impair normal cellular functions. Recent advancements in the field of aging have shown that targeting senescent cells for clearance has resulted in the restoration of physiological health and hindrance of aging. For effective approaches, the right cells need to be targeted. Historically, cells were tagged to be senescent based on simple assays that focused on the possession of one, or only a few, traits. Newer studies have shown that senescent cells have characteristics that vary among individuals and thus no universal classification system exists, making it hard to confidently identify senescence. Through novel immunofluorescence imaging and quantitative protein analysis, we found certain biomarkers that reveal the temporal dynamics of senescence induction and maturation. We also reveal that cells can be viewed as “more” senescent than others, as evident by varied expressions of proteins associated with the senescent phenotype. This phenotypic scale of depth has shown to be influenced by factors such as proximity to other cells and contents within extracellular matrix environments. Our work will contribute to a deeper understanding of how this cell state arises and presents itself, which will lead to improvements in therapies that combat aging and its associated diseases.
Madeline Loops (Sun,) studied this question.