The Yin–Yang of Stress and Senescence: Integrated Stress Response and SASP Crosstalk in Stem Cell Fate, Regeneration, and Disease

The document explores the dual roles of the integrated stress response (ISR) and the senescence-associated secretory phenotype (SASP) in stem cell fate, highlighting their Yin-Yang dynamic. Transient ISR and acute SASP promote beneficial outcomes like adaptation and regeneration, while chronic ISR and unresolved SASP lead to negative effects such as stem cell exhaustion and tumorigenesis. Mechanistically, ISR influences translational control, and SASP alters the extracellular environment, with their interaction shaping tissue niches and stem cell potential. Understanding this balance offers insights into regenerative medicine, anti-aging, and cancer therapies.