Cell Senescence, DNA Damage, and Metabolism

Significance: Senescence is an essential biological process that blocks tumorigenesis, limits tissue damage, and aids embryonic development. However, once senescent cells accumulate in tissues during aging, they promote the development of age-related diseases and limit health span. Thus, it is essential to expand the boundaries of our knowledge about the mechanisms responsible for controlling cellular senescence. Recent Advances: Cellular metabolism plays a significant role in the regulation of various signaling processes involved in cell senescence. In the past decade, our knowledge about the interplay between cell signaling, cell metabolism, and cellular senescence has significantly expanded. Critical Issues: In this study, we review metabolic pathways in senescent cells and the impact of these pathways on the response to DNA damage and the senescence-associated secretory phenotype. Future Directions: Future research should elucidate metabolic mechanisms that promote specific alterations in senescent cell phenotype, with a final goal of developing a new therapeutic strategy. Antioxid. Redox Signal. 34, 324–334.