Current Understanding of p53-Dependent Cellular Senescence in Health Disparities: Molecular Insights and Public-Health Strategies

Disadvantaged populations age faster and develop chronic disease earlier, but the molecular conduit from social adversity to biology is not fully defined. This review synthesizes molecular, epidemiological, and policy evidence along a single axis: p53-governed cellular senescence. Genomic and metabolic stress stabilize p53, induce p21-mediated cell cycle arrest, and trigger a pro-inflammatory secretory program that compromises tissue function. Conditions concentrated in communities with limited resources, such as, air pollution, ultra-processed diets, chronic stress, and obesity activate these pathways and expand senescent populations in vascular, metabolic, and immune tissues, amplifying atherosclerosis, insulin resistance, and cancer progression. Senolytics (dasatinib plus quercetin, navitoclax, and fisetin) and senomorphics (metformin and rapamycin) show early benefit signals, but translation must be equity-first. The next step is to conduct community-engaged, cluster-randomized pilots that pair senotherapeutics with neighborhood exposure abatement, use co-primary endpoints (multi-omic senescence signatures plus exposure indices), stratify by deprivation, apply adaptive dosing, and track affordability and access, yielding decision rules for scalable, equity-ready implementation.