Abstract
BACKGROUND: Sickle cell disease (SCD) is a chronic medical condition characterized by red blood cell sickling, vaso-occlusion, hemolytic anemia, and subsequently, end-organ damage and reduced survival. Because of this significant pathophysiology and early mortality, we hypothesized that patients with SCD are experiencing accelerated biological aging compared with individuals without SCD. METHODS: We utilized the DunedinPACE measure to compare the epigenetic pace of aging in 131 Black Americans with SCD to 1391 Black American veterans without SCD. RESULTS: SCD patients displayed a significantly accelerated pace of aging (DunedinPACE mean difference of 0.057 points) compared with the veterans without SCD, whereby SCD patients were aging ≈0.7 months more per year than those without SCD (p = 4.49 × 10-8). This was true, even though the SCD patients were significantly younger according to chronological age than the individuals without SCD, making the epigenetic aging discrepancy even more apparent. This association became stronger when we removed individuals with posttraumatic stress disorder from the non-SCD group (p = 2.18 × 10-9), and stronger still when we restricted the SCD patients to those with hemoglobin SS and Sβ0 thalassemia genotypes (p = 1.61 × 10-10). CONCLUSIONS: These data support our hypothesis that individuals with SCD experience accelerated biological aging as measured by global epigenetic variation. The assessment of epigenetic measures of biological aging may prove useful to identify which SCD patients would most benefit from clinical interventions to reduce mortality.