Senescent cells at the crossroads of aging, disease, and tissue homeostasis

Originally identified as an outcome of continuous culture of primary cells, cellular senescence has moved beyond the culture dish and is now a bona fide driver of aging and disease in animal models, and growing links to human disease. This cellular stress response consists of a stable proliferative arrest coupled to multiple phenotypic changes. Perhaps the most important of these is the senescence-associated secretory phenotype, or senescence-associated secretory phenotype -a complex and variable collection of secreted molecules release by senescent cells with a number of potent biological activities. Senescent cells appear in multiple age-associated conditions in humans and mice, and interventions that eliminate these cells can prevent or even reverse multiple diseases in mouse models. Here, we review salient aspects of senescent cells in the context of human disease and homeostasis. Senescent cells increase in abundance during several diseases that associated with premature aging. Conversely, senescent cells have a key role in beneficial processes such as development and wound healing, and thus can help maintain tissue homeostasis. Finally, we speculate on mechanisms by which deleterious aspects of senescent cells might be targeted while retaining homeostatic aspects in order to improve age-related outcomes. Originally identified as a phenotype adopted by cultured cells during replicative exhaustion, cellular senescence has expanded beyond the culture dish and is now a recognized driver of aging. However, the physiological role of senescence is complex, promoting tissue homeostasis or driving pathology depending on context. Kuehnemann and Wiley review the physiological role of senescent cells in the context of disease drivers of aging and tissue homeostasis, with an eye toward targeting the complexity of senescence to distinguish between these processes.image