2018 | Hernandez-Segura, Alejandra; Nehme, Jamil; Demaria, Marco
The article "Hallmarks of Cellular Senescence" by Hernandez-Segura, Nehme, and Demaria discusses the molecular regulators and phenotypic characteristics of cellular senescence, a state of permanent cell cycle arrest that can promote tissue remodeling during development and after injury but also contribute to tissue decline, inflammation, and tumorigenesis in aged organisms. The authors highlight the complexity of the senescence phenotype, which includes features such as chronic DNA damage response (DDR), enhanced secretion of proinflammatory and tissue-remodeling factors, altered metabolic rates, and endoplasmic reticulum (ER) stress. They emphasize the challenges in identifying universal or program-specific markers for senescent cells due to the heterogeneity and dynamic nature of senescence programs. The article also reviews methods for detecting senescent cells, including the measurement of DDR, cell cycle arrest, secretory phenotype, apoptosis resistance, metabolism, and ER stress. Additionally, it discusses the role of the senescence-associated secretory phenotype (SASP) and the potential therapeutic targets for interventions targeting senescent cells, such as senolytics and SASP inhibitors. The authors conclude by noting the ongoing efforts to identify and characterize senescent cells to develop effective interventions for aging-related diseases.The article "Hallmarks of Cellular Senescence" by Hernandez-Segura, Nehme, and Demaria discusses the molecular regulators and phenotypic characteristics of cellular senescence, a state of permanent cell cycle arrest that can promote tissue remodeling during development and after injury but also contribute to tissue decline, inflammation, and tumorigenesis in aged organisms. The authors highlight the complexity of the senescence phenotype, which includes features such as chronic DNA damage response (DDR), enhanced secretion of proinflammatory and tissue-remodeling factors, altered metabolic rates, and endoplasmic reticulum (ER) stress. They emphasize the challenges in identifying universal or program-specific markers for senescent cells due to the heterogeneity and dynamic nature of senescence programs. The article also reviews methods for detecting senescent cells, including the measurement of DDR, cell cycle arrest, secretory phenotype, apoptosis resistance, metabolism, and ER stress. Additionally, it discusses the role of the senescence-associated secretory phenotype (SASP) and the potential therapeutic targets for interventions targeting senescent cells, such as senolytics and SASP inhibitors. The authors conclude by noting the ongoing efforts to identify and characterize senescent cells to develop effective interventions for aging-related diseases.