From Development to Aging: The Path to Cellular Senescence

Significance: Senescence is a cellular state induced by internal or external stimuli, which result in cell cycle arrest, morphological changes, and dysfunctions in mitochondrial and lysosomal functionality as well as the senescence-associated secretory phenotype. Senescent cells accumulate in tissues in physiological and pathological conditions such as development, tissue repair, aging, and cancer. Recent Advances: Growing evidences indicate that senescent cells in vivo are a heterogeneous cell population due to different cell-autonomous activated pathways and distinct microenvironmental contexts. Critical Issues: In this review, we discuss the different contexts where senescence assumes a key role with beneficial or harmful outcomes. The heterogeneous nature of senescence pushes toward resolution of the specific molecular profile and secretome to typify senescent cells in physiological and pathological contexts. Future Directions: Future research will enable exploring the heterogeneity of the senescent population to precisely map the progression of cells through senescent trajectories and study the impact of the therapeutic advantage of senolytic drugs for translational strategies toward supporting the health span.

Automated summary

Senescence is a cellular state induced by internal or external stimuli, resulting in cell cycle arrest, morphological changes, and dysfunctions in mitochondrial and lysosomal functionality. Recent evidence suggests that senescent cells in vivo are a heterogeneous cell population due to different activated pathways and distinct microenvironmental contexts. Future research will focus on exploring the heterogeneity of senescent cells to map cell progression and study the therapeutic advantages of senolytic drugs.