The Impact of Aging on Organ Systems in Sickle Cell Disease: a Comparative Review of Physiological Adaptation and Dysfunction

Sickle cell anemia (SCA) is a progressive, systemic disorder that can lead to multi-organ dysfunction. While it has traditionally been most prevalent in regions where malaria is endemic, recent epidemiological studies have shown an increasing disease prevalence in non-endemic areas, primarily attributed to global human migration patterns. The severity of SCA typically worsens with age. In early childhood, affected individuals may present with renal hyperfiltration, neurocognitive delays, cardiac remodeling, and skeletal fragility. The presence of these early manifestations often predicts the development of chronic complications later in life, including splenic atrophy, neurodegeneration, and impaired cerebral perfusion. Adequate management of SCA begins with universal newborn screening programs, enabling early detection and the initiation of appropriate interventions. Therapeutic advancements, ranging from disease-modifying agents such as hydroxyurea to curative options including gene therapy and stem cell transplantation, have significantly improved clinical outcomes; however, long-term morbidity remains a significant challenge. This review aimed to explore the effect of aging on pathophysiological changes and the onset of organ-specific complications in SCA patients. It highlights the importance of age-tailored monitoring and a multidisciplinary approach to detect early signs of organ damage, prevent irreversible complications, and consequently improve overall quality of life.